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PubMed2006

Regulation of NKG2D ligand gene expression.

The activating immunoreceptor NKG2D has seven known host ligands encoded by the MHC class I chain-related MIC and ULBP/RAET genes. Why there is such diversity of NKG2D ligands is not known but one hypothesis is that they are differentially expressed in different tissues in response to different stresses. To explore this, we compared expression patterns and promoters of NKG2D ligand genes. ULBP/RAET genes were transcribed independent of each other in a panel of cell lines. ULBP/RAET gene expression was upregulated on infection with human cytomegalovirus; however, a clinical strain, Toledo, induced expression more slowly than did a laboratory strain, AD169. ULBP4/RAET1E was not induced by infection with either strain. To investigate the mechanisms behind the similarities and differences in NKG2D ligand gene expression a comparative sequence analysis of NKG2D ligand gene putative promoter regions was conducted. Sequence alignments demonstrated that there was significant sequence diversity; however, one region of high similarity between most of the genes is evident. This region contains a number of potential transcription factor binding sites, including those involved in shock responses and sites for retinoic acid-induced factors. Promoters of some NKG2D ligand genes are polymorphic and several sequence alterations in these alleles abolished putative transcription factor binding.

Alleles↗
PubMed1992

DNA diversity among clinical isolates of Helicobacter pylori detected by PCR-based RAPD fingerprinting.

The RAPD (or AP-PCR) DNA fingerprinting method was used to distinguish among clinical isolates of Helicobacter pylori, a bacterium whose long term carriage is associated with gastritis, peptic ulcers and gastric carcinomas. This method uses arbitrarily chosen oligonucleotides to prime DNA synthesis from genomic sites to which they are fortuitously matched, or almost matched. Most 10-nt primers with > or = 60% G + C yielded strain-specific arrays of up to 15 prominent fragments, as did most longer (> or = 17-nt) primers, whereas most 10-nt primers with 50% G+C did not. Each of 64 independent H. pylori isolates, 60 of which were from patients in the same hospital, was distinguishable with a single RAPD primer, which suggests a high level of DNA sequence diversity within this species. In contrast, isolates from initial and followup biopsies were indistinguishable in each of three cases tested.

Animals↗
PubMed1997

The wheat protein kinase gene, TaPK3, of the PKABA1 subfamily is differentially regulated in greening wheat seedlings.

We have identified a new wheat PKABA1-like protein kinase gene, TaPK3, that is expressed in greening wheat seedlings. TaPK3 has high sequence homology (97% similarity with some sequence diversity at the 3' end) to the wheat PKABA1 protein kinase mRNA, which is upregulated by cold-temperature treatment, dehydration and abscisic acid (ABA). Use of a TaPK3 gene-specific probe has revealed that TaPK3 is differentially expressed with respect to PKABA1. TaPK3 mRNA accumulates in greening shoot tissue of wheat, but is not affected by dehydration, cold-temperature treatment or ABA. Based on sequence and expression differences, we conclude that expression of the PKABA1-like protein kinases is not limited to stress responses.

Amino Acid Sequence↗
PubMed1991

An NF-kappa B-like transcription factor mediates IL-1/TNF-alpha induction of gro in human fibroblasts.

Normal human foreskin fibroblasts were used to examine transcriptional induction by IL-1 and TNF-alpha of the novel cytokine gro (melanoma growth-stimulating activity). Gro mRNA was expressed at levels 100-fold above background within 45 min of exposure to either IL-1 or TNF-alpha, in growing or serum-starved cells and a similar response was shown by IL-6. In contrast, as shown previously, gro mRNA was elevated only 10-fold by serum in starved but not in growing cells, similar to fos. Thus gro expression appears to be regulated by at least two signal transduction systems: a cytokine pathway, and a growth-related pathway. Three closely related gro genes (alpha, beta, and gamma) have been described. Their proximal 5' regulatory sequences presented here show close similarity in the region to -136, which includes the NF-kappa B site at -66 to -76 in gro alpha and gro gamma, and -64 to -74 in gro beta, and sequence diversity further upstream. Transient transfection of HeLa cells with CAT constructs localized the cytokine response to a region between -84 and -65 in gro beta. Gel retardation studies with FS-2 cells identified a cytokine-induced protein binding at the NF-kappa B site in all three gro genes as shown by competition studies with a pair of oligonucleotides representing wild-type and mutant sequences of the NF-kappa B binding site. Neither serum nor PMA induced a detectable gel shift at NF-kappa B or upstream to position -723. These results demonstrate conservation of the cytokine response element, NF-kappa B, in the three genes, consistent with the conservation of sequence in this region; and suggest that differential expression of the three gro genes may depend upon interactions with other sites located in the divergent upstream region.

Base Sequence↗
PubMed1993

Analysis of feline calicivirus capsid protein genes: identification of variable antigenic determinant regions of the protein.

Three isolates of feline calicivirus (FCV) designated NADC, KCD and CFI/68 were compared for biochemical, serological and genetic variation within the capsid protein gene. The M(r) of the capsid protein from purified virions was approximately 66,000 for the NADC virus isolate, which differed slightly from the relative mobilities of the purified capsid proteins of the KCD and CFI/68 isolates. Polyclonal antisera from either cats infected or rabbits hyperimmunized with the CFI/68 isolate cross-reacted with all three isolates by Western blot analysis. However, these polyclonal antisera to CFI/68 varied considerably in their virus-neutralization titres to the KCD and NADC isolates. Nucleotide sequence data confirmed the genetic variability among these FCV isolates. Comparison of the predicted amino acid sequence of the capsid protein among isolates revealed two regions of sequence divergence that probably contain the antigenically variable determinants. These hypervariable regions may vary by as much as 55% among isolates of FCV. The amino acid sequence diversity in the hypervariable regions of the KCD and NADC isolates correlated well with the virus-neutralization data and suggests that polyvalent vaccines may be more protective than the commonly used monovalent vaccines.

Amino Acid Sequence↗
PubMed2001

Immunological and biochemical characterization of streptococcal pyrogenic exotoxins I and J (SPE-I and SPE-J) from Streptococcus pyogenes.

Recently, we described the identification of novel streptococcal superantigens (SAgs) by mining the Streptococcus pyogenes M1 genome database at Oklahoma University. Here, we report the cloning, expression, and functional analysis of streptococcal pyrogenic exotoxin (SPE)-J and another novel SAg (SPE-I). SPE-I is most closely related to SPE-H and staphylococcal enterotoxin I, whereas SPE-J is most closely related to SPE-C. Recombinant forms of SPE-I and SPE-J were mitogenic for PBL, both reaching half maximum responses at 0.1 pg/ml. Evidence from binding studies and cell aggregation assays using a human B-lymphoblastoid cell line (LG-2) suggests that both toxins exclusively bind to the polymorphic MHC class II beta-chain in a zinc-dependent mode but not to the generic MHC class II alpha-chain. The results from analysis by light scattering indicate that SPE-J exists as a dimer in solution above concentrations of 4.0 mg/ml. Moreover, SPE-J induced a rapid homotypic aggregation of LG-2 cells, suggesting that this toxin might cross-link MHC class II molecules on the cell surface by building tetramers of the type HLA-DRbeta-SPE-J-SPE-J-HLA-DRbeta. SPE-I preferably stimulates T cells bearing the Vbeta18.1 TCR, which is not targeted by any other known SAG: SPE-J almost exclusively stimulates Vbeta2.1 T cells, a Vbeta that is targeted by several other streptococcal SAgs, suggesting a specific role for this T cell subpopulation in immune defense. Despite a primary sequence diversity of 51%, SPE-J is functionally indistinguishable from SPE-C and might play a role in streptococcal disease, which has previously been addressed to SPE-C.

Amino Acid Sequence↗
PubMed2005

Efficient construction of a highly useful phage-displayed human antibody repertoire.

We have constructed a highly useful phage-displayed human antibody repertoire with limited cloning efforts. Our strategy was to maximize diversity during the first steps of library construction through the use of various lymphoid sources from several donors, inclusion of different immunoglobulin isotypes, and performance of multiple separate amplification reactions with all possible combinations within a complex primer set. The resulting variable region collections were cloned to form a moderate size library, composed by 4.25x10(8) single chain antibody fragments. This repertoire was successfully used to retrieve binders to seven model antigens: six proteins and one 12 aa peptide. Binding affinities reached nanomolar and even subnanomolar range. Sequence diversity and V-gene usage variability among binders were proven. Our approach was not focused on absolute library size, but on a high quality sampling of variable regions from the human antibody repertoire.

Amino Acid Sequence↗
PubMed1994

Molecular genetic basis of allelic polymorphism in malate dehydrogenase (mdh) in natural populations of Escherichia coli and Salmonella enterica.

Nucleotide sequences of the mdh gene encoding the metabolic enzyme malate dehydrogenase (MDH) were determined for 44 strains representing the major lineages of Escherichia coli and the eight subspecies of Salmonella enterica. Sequence diversity was four times greater in S. enterica than in E. coli, and in both species the rate of amino acid substitution was lower in the NAD(+)-binding domain than in the catalytic domain. Divergence of the mdh genes of the two species apparently has not involved excess nonsynonymous substitutions resulting from the fixation of adaptive amino acid mutations. Allozyme analysis detected 57% of the distinctive amino acid sequences. Statistical tests of the distribution of polymorphic synonymous nucleotide sites identified four possible intragenic recombination events, one involving a single allele of E. coli and three involving alleles of the three subspecies of S. enterica. But recombination at mdh has not occurred with sufficient frequency to obscure the phylogenetic relationships among strains indicated by multilocus enzyme electrophoresis, total DNA hybridization, and sequence analysis of the gapA and putP genes. These findings provide further evidence that the effective (realized) rates of horizontal transfer and recombination for metabolic enzyme and other housekeeping genes are generally low in these species, in contrast to those for loci encoding or mediating the structure of cell-surface and other macromolecules for which recombinants may be subject to strong balancing, directional, or diversifying selection.

Adaptation, Physiological↗
PubMed2006

Neurologic disease in captive lions (Panthera leo) with low-titer lion lentivirus infection.

Lion lentivirus (LLV; also known as feline immunodeficiency virus of lion, Panthera leo [FIVPle]) is present in free-ranging and captive lion populations at a seroprevalence of up to 100%; however, clinical signs are rarely reported. LLV displays up to 25% interclade sequence diversity, suggesting that it has been in the lion population for some time and may be significantly host adapted. Three captive lions diagnosed with LLV infection displayed lymphocyte subset alterations and progressive behavioral, locomotor, and neuroanatomic abnormalities. No evidence of infection with other potential neuropathogens was found. Antemortem electrodiagnostics and radiologic imaging indicated a diagnosis consistent with lentiviral neuropathy. PCR was used to determine a partial lentiviral genomic sequence and to quantify the proviral burden in eight postmortem tissue specimens. Phylogenetic analysis demonstrated that the virus was consistent with the LLV detected in other captive and free-ranging lions. Despite progressive neurologic signs, the proviral load in tissues, including several regions of the brain, was low; furthermore, gross and histopathologic changes in the brain were minimal. These findings suggest that the symptoms in these animals resulted from nonspecific encephalopathy, similar to human immunodeficiency virus, FIV, and simian immunodeficiency virus (SIV) neuropathies, rather than a direct effect of active viral replication. The association of neuropathy and lymphocyte subset alterations with chronic LLV infection suggests that long-term LLV infection can have detrimental effects for the host, including death. This is similar to reports of aged sootey mangabeys dying from diseases typically associated with end-stage SIV infection and indicates areas for further research of lentiviral infections of seemingly adapted natural hosts, including mechanisms of host control and viral adaptation.

Animals↗
PubMed2004

Alternative approaches for efficient inhibition of hepatitis C virus RNA replication by small interfering RNAs.

Persistent infection with hepatitis C virus (HCV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. It has recently been shown that HCV RNA replication is susceptible to small interfering RNAs (siRNAs), but the antiviral activity of siRNAs depends very much on their complementarity to the target sequence. Thus, the high degree of sequence diversity between different HCV genotypes and the rapid evolution of new quasispecies is a major problem in the development of siRNA-based gene therapies. For this study, we developed two alternative strategies to overcome these obstacles. In one approach, we used endoribonuclease-prepared siRNAs (esiRNAs) to simultaneously target multiple sites of the viral genome. We show that esiRNAs directed against various regions of the HCV coding sequence as well as the 5' nontranslated region (5' NTR) efficiently block the replication of subgenomic and genomic HCV replicons. In an alternative approach, we generated pseudotyped retroviruses encoding short hairpin RNAs (shRNAs). A total of 12 shRNAs, most of them targeting highly conserved sequence motifs within the 5' NTR or the early core coding region, were analyzed for their antiviral activities. After the transduction of Huh-7 cells containing a subgenomic HCV replicon, we found that all shRNAs targeting sequences in domain IV or nearby coding sequences blocked viral replication. In contrast, only one of seven shRNAs targeting sequences in domain II or III had a similar degree of antiviral activity, indicating that large sections of the NTRs are resistant to RNA interference. Moreover, we show that naive Huh-7 cells that stably expressed certain 5' NTR-specific shRNAs were largely resistant to a challenge with HCV replicons. These results demonstrate that the retroviral transduction of HCV-specific shRNAs provides a new possibility for antiviral intervention.

Antiviral Agents↗
PubMed2001

The evolution of Ty1-copia group retrotransposons in gymnosperms.

A diverse collection of Ty1-copia group retrotransposons has been characterized from the genome of Picea abies (Norway spruce) by degenerate PCR amplification of a region of the reverse transcriptase gene. The occurrence of these retrotransposable elements in the gymnosperms was investigated by Southern blot hybridization analysis. The distribution of the different retrotransposons across the gymnosperms varies greatly. All of the retrotransposon clones isolated are highly conserved within the Picea (spruce) genus, many are also present in Pinus (pine) and/or Abies (fir) genera, and some share strongly homologous sequences with one or more of cedar, larch, Sequoia, cypress, and Ginkgo. Further subclones of one of the most strongly conserved retrotransposon sequences, Tpa28, were obtained from Ginkgo and P. abies. Comparisons of individual sequence pairs between the two species show nucleotide cross-homologies of around 80%-85%, corresponding to nucleotide substitution rates similar to those of nuclear protein-coding genes. Analysis of Tpa28 consensus sequences reveals that strong purifying selection has acted on this retrotransposon in the lineages connecting Ginkgo and Picea. Collectively, these data suggest, first, that the evolution of the Ty1-copia retrotransposon group in the gymnosperms is dominated by germ line vertical transmission, with strong selection for reverse transcriptase sequence, and, second, that extinction of individual retrotransposon types has been comparatively rare in gymnosperm species lineages compared with angiosperms. If this very high level of sequence conservation is a general property of the retrotransposons, then their extreme sequence diversity implies that they are extremely ancient, and the major element lineages seen today may have arisen early in eukaryote evolution. The data are also consistent with horizontal transmission of particular retrotransposons between species, but such a mechanism is unnecessary to explain the results.

Amino Acid Sequence↗
PubMed2004

Electrophoretic variants of cardiac myosin heavy chain-alpha in Sprague Dawley rats.

Analysis of cardiac myosin revealed differences in gel electrophoretic migration patterns of the alpha-isoform of myosin heavy chain, but not the beta-isoform, in Sprague Dawley rats. No differences in the migration patterns of the alpha-or beta-isoforms were observed in other rat strains. Three electrophoretic migration patterns of the alpha-isoforms were observed in individual rats: a slower migrating isoform alone (4% of all rats tested), a faster migrating isoform alone (55%), and both isoforms (41%). The isoform expression pattern was identical in all myocardial regions in each rat. Frequency of expression patterns suggests multiple gene sequences for alpha-cardiac myosin heavy chain in Sprague Dawley rats. Sequence analysis of amplified regions of the Sprague Dawley and Brown Norway rat alpha-myosin genes, specifically the 5'-untranslated region, exons 1-3, and associated introns, showed numerous single nucleotide polymorphisms in coding and noncoding regions, including putative regulatory sites in Sprague Dawley rats, but not in Brown Norway rats. All Sprague Dawley rats varied from Brown Norway rats and no heterogeneity was observed in Brown Norway rats. Several deletions and dimorphic positions were also observed. Dimorphic positions were evident on automated sequencing comparisons. The data indicate that at least two alpha-myosin heavy chain isoforms exist in Sprague Dawley rats and these rats exhibit sequence diversity within that portion of the alpha-myosin heavy chain gene reported in this study.

Animals↗
PubMed1996

Crystal structure of a new heat-labile enterotoxin, LT-IIb.

BACKGROUND: Cholera toxin from Vibrio cholerae and the type I heat-labile enterotoxins (LT-Is) from Escherichia coli are oligomeric proteins with AB5 structures. The type II heat-labile enterotoxins (LT-IIs) from E. coli are structurally similar to, but antigenically distinct from, the type I enterotoxins. The A subunits of type I and type II enterotoxins are homologous and activate adenylate cyclase by ADP-ribosylation of a G protein subunit, G8 alpha. However, the B subunits of type I and type II enterotoxins differ dramatically in amino acid sequence and ganglioside-binding specificity. The structure of LT-IIb was determined both as a prototype for other LT-IIs and to provide additional insights into structure/function relationships among members of the heat-labile enterotoxin family and the superfamily of ADP-ribosylating protein toxins. RESULTS: The 2.25 A crystal structure of the LT-IIb holotoxin has been determined. The structure reveals striking similarities with LT-I in both the catalytic A subunit and the ganglioside-binding B subunits. The latter form a pentamer which has a central pore with a diameter of 10-18 A. Despite their similarities, the relative orientation between the A polypeptide and the B pentamer differs by 24 degrees in LT-I and LT-IIb. A common hydrophobic ring was observed at the A-B5 interface which may be important in the cholera toxin family for assembly of the AB5 heterohexamer. A cluster of arginine residues at the surface of the A subunit of LT-I and cholera toxin, possibly involved in assembly, is also present in LT-IIb. The ganglioside receptor binding sites are localized, as suggested by mutagenesis, and are in a position roughly similar to the sites where LT-I binds its receptor. CONCLUSIONS: The structure of LT-IIb provides insight into the sequence diversity and structural similarity of the AB5 toxin family. New knowledge has been gained regarding the assembly of AB5 toxins and their active-site architecture.

Amino Acid Sequence↗
PubMed2006

Prevalence and evolution of core photosystem II genes in marine cyanobacterial viruses and their hosts.

Cyanophages (cyanobacterial viruses) are important agents of horizontal gene transfer among marine cyanobacteria, the numerically dominant photosynthetic organisms in the oceans. Some cyanophage genomes carry and express host-like photosynthesis genes, presumably to augment the host photosynthetic machinery during infection. To study the prevalence and evolutionary dynamics of this phenomenon, 33 cultured cyanophages of known family and host range and viral DNA from field samples were screened for the presence of two core photosystem reaction center genes, psbA and psbD. Combining this expanded dataset with published data for nine other cyanophages, we found that 88% of the phage genomes contain psbA, and 50% contain both psbA and psbD. The psbA gene was found in all myoviruses and Prochlorococcus podoviruses, but could not be amplified from Prochlorococcus siphoviruses or Synechococcus podoviruses. Nearly all of the phages that encoded both psbA and psbD had broad host ranges. We speculate that the presence or absence of psbA in a phage genome may be determined by the length of the latent period of infection. Whether it also carries psbD may reflect constraints on coupling of viral- and host-encoded PsbA-PsbD in the photosynthetic reaction center across divergent hosts. Phylogenetic clustering patterns of these genes from cultured phages suggest that whole genes have been transferred from host to phage in a discrete number of events over the course of evolution (four for psbA, and two for psbD), followed by horizontal and vertical transfer between cyanophages. Clustering patterns of psbA and psbD from Synechococcus cells were inconsistent with other molecular phylogenetic markers, suggesting genetic exchanges involving Synechococcus lineages. Signatures of intragenic recombination, detected within the cyanophage gene pool as well as between hosts and phages in both directions, support this hypothesis. The analysis of cyanophage psbA and psbD genes from field populations revealed significant sequence diversity, much of which is represented in our cultured isolates. Collectively, these findings show that photosynthesis genes are common in cyanophages and that significant genetic exchanges occur from host to phage, phage to host, and within the phage gene pool. This generates genetic diversity among the phage, which serves as a reservoir for their hosts, and in turn influences photosystem evolution.

Base Composition↗
PubMed1994

Molecular characterization of human Ig heavy chain DIR genes.

Antibody VDJ recombination is ensured by evolutionarily conserved recombination signals (RS). The 12/23 rule postulates that only gene segments with asymmetrically spaced RS recombine with one another. Two unusually long D genes (170 bp) with irregular RS (DIR) have been reported in humans and have been postulated to participate actively in VDJ recombination, thus frequently contributing to the Ab heavy chain third hypervariable region (CDR3). However, the limited sequence information retained in the CDR3 along with significant sequence diversity has precluded an accurate assessment of the actual role and genomic diversity of DIR genes. Furthermore, DIR genes pose an interesting puzzle in terms of their precise mechanism of recombination because they possess multiple and imperfect RS, often located up to 30 bp away from the recombining fragment within the DIR coding region. Here we present conclusive evidence for the existence of additional human germ-line DIR genes and preliminary evidence that suggests the absence of DIR-like sequences in nonprimate animals. We also show that DIR genes are under the transcriptional control of VH-independent promoters and have the potential to encode a D mu protein of 105 amino acids. Finally, DIR genes seem at least in early fetal life to recombine preferentially through the conventional 3' RS.

Animals↗
PubMed2003

FHA domains as phospho-threonine binding modules in cell signaling.

Forkhead-associated (FHA) domains are present in >200 diverse proteins in all phyla from bacteria to mammals and seem to be particularly prevalent in proteins with cell cycle control functions. Recent work from several laboratories has considerably improved our understanding of the structure and function of these domains that were virtually unknown a few years ago, and the first disease associations of FHA domains have now emerged. FHA domains form 11-stranded beta-sandwiches that contain some 100-180 amino acid residues with a high degree of sequence diversity. FHA domains act as phosphorylation-dependent protein-protein interaction modules that preferentially bind to phospho-threonine residues in their targets. Interestingly, point mutations in the human CHK2 gene that lead to single-residue amino acid substitutions in the FHA domain of this cell cycle checkpoint kinase have been found to cause a subset of cases of the Li-Fraumeni multi-cancer syndrome.

Amino Acid Sequence↗
PubMed2003

Napoleon Bonaparte and the fate of an Amazonian rat: new data on the taxonomy of Mesomys hispidus (Rodentia: Echimyidae).

The spiny rat Mesomys hispidus is one of many South American rodents that lack adequate taxonomic definition. The few sampled populations of this broadly distributed trans-Amazonian arboreal rat have come from widely separated regions and are typically highly divergent. The holotype was described in 1817 by A.-G. Desmarest, after Napoleon's army brought it to Paris following the plunder of Lisbon in 1808; however, the locality of origin has remained unknown. Here we examine the taxonomic status of this species by direct comparison of 50 extant individuals with the holotype at the morphometric and genetic levels, the latter based on 331 bp of the mitochondrial cytochrome b gene retrieved from a small skin fragment of the holotype with ancient DNA technology. Extensive sequence divergence is present among samples of M. hispidus collected from throughout its range, from French Guiana across Amazonia to Bolivia and Peru, with at least seven mitochondrial clades recognized (average divergence of 7.7% Kimura 2-parameter distance). Sequence from the holotype is, however, only weakly divergent from those of recent samples from French Guiana. Moreover, the holotype clusters with greater that 99% posterior probability with samples from this part of Amazonia in a discriminant analysis based on 22 cranial and dental measurements. Thus, we suggest that the holotype was originally obtained in eastern Amazonia north of the Amazon River, most likely in the Brazilian state of Amapá. Despite the high level of sequence diversity and marked morphological differences in size across the range of M. hispidus, we continue to regard this assemblage as a single species until additional samples and analyses suggest otherwise.

Animals↗
PubMed2006

Crystal structure of SUMO-3-modified thymine-DNA glycosylase.

Modification of cellular proteins by the small ubiquitin-like modifier SUMO is important in regulating various cellular events. Many different nuclear proteins are targeted by SUMO, and the functional consequences of this modification are diverse. For most proteins, however, the functional and structural consequences of modification by specific SUMO isomers are unclear. Conjugation of SUMO to thymine-DNA glycosylase (TDG) induces the dissociation of TDG from its product DNA. Structure determination of the TDG central region conjugated to SUMO-1 previously suggested a mechanism in which the SUMOylation-induced conformational change in the C-terminal region of TDG releases TDG from tight binding to its product DNA. Here, we have determined the crystal structure of the central region of TDG conjugated to SUMO-3. The overall structure of SUMO-3-conjugated TDG is similar to the previously reported structure of TDG conjugated to SUMO-1, despite the relatively low level of amino acid sequence similarity between SUMO-3 and SUMO-1. The two structures revealed that the sequence of TDG that resembles the SUMO-binding motif (SBM) can form an intermolecular beta-sheet with either SUMO-1 or SUMO-3. Structural comparison with the canonical SBM shows that this SBM-like sequence of TDG retains all of the characteristic interactions of the SBM, indicating sequence diversity in the SBM.

Amino Acid Sequence↗