HIV expression levels ex vivo: a surrogate marker for clinical endpoints in the evaluation of AIDS treatments?
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
W Saurin
Publications and source records attributed to W Saurin.
Comparison of sequences from the malB regions of Salmonella typhimurium and Enterobacter aerogenes with Escherichia coli K12: a potential new regulatory site in the interoperonic region.
The malE and malK genes from Salmonella typhimurium, and the malEFG operon and a portion of malK from Enterobacter aerogenes were cloned and sequenced. Plasmid-borne malE genes from both species and the malF and malG genes from E. aerogenes were expressed normally in Escherichia coli, and their products function in maltose transport. This shows that the malB products from the three species are interchangeable, at least in the combinations tested. The general genetic organization of the malB region is conserved. Potential binding sites and distances between them are highly conserved in the regulatory intervals. An unexpected conserved region was detected, which we call the U box, and which could be another target for a regulatory protein. This hypothesis is supported by the presence of the U box in the regulatory region of the pulA-malX operon in Klebsiella pneumoniae. The intergenic region between malE and malF from S. typhimurium and E. aerogenes, contains inverted repeats similar to the palindromic units (PU or REP) found at the same location in E. coli. The predicted amino acid sequence of the encoded proteins showed 90% or more identity in every pairwise comparison of species.
Amino Acid Sequence↗
Periplasmic binding protein dependent transport system for maltose and maltodextrins: some recent studies.
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Amino Acid Sequence↗
HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions.
RNA viruses are renowed for their genetic variability. The human immunodeficiency viruses (HIV) are no exception. A rapid method has been established for the genetic identification and differentiation of viral strains based on the sequencing of many M13 clones of gene-amplified products. Some isolates are internally relatively homogeneous while others are heterogeneous. There was no correlation between virus complexity and disease stage. One isolate was in fact a mixture of two distinct strains. A strong preference for G----A base substitutions was observed. These data indicate that HIV isolates cannot be described in simple molecular terms and should rather be considered as quasispecies.
Amino Acid Sequence↗
Versatility of a vector for expressing foreign polypeptides at the surface of gram-negative bacteria.
A wide variety of peptides in terms of length and sequence can be expressed at the surface of the bacterium Escherichia coli by genetic insertion into a 'permissive' site of the outer membrane protein LamB, used as a carrier. The resulting hybrid proteins essentially keep their biological activities with inserts of up to about 60 amino acid residues, and of a large range of predicted structures or hydrophobicities. This reflects a remarkable flexibility in the organization of the protein, but also in the export machinery. The method used to select such a permissive site is quite general and its potential to generate applications, including a versatile type of live bacterial vaccine, are discussed.
Amino Acid Sequence↗
RNA polymerases B and C are more closely related to each other than to RNA polymerase A.
Amino acid sequence comparison of the largest subunit of the three forms of yeast nuclear RNA polymerase disclosed six major conserved regions that are partly retained in the cognate subunits from bacteria, viral, and insect enzymes (Mémet, S., Gouy, M., Marck, C., Sentenac, A., and Buhler, J.-M. (1988) J. Biol. Chem. 263, 2830-2839). Within these conserved domains, the high sequence similarity of B220 and C160 subunits (52% identity) sets them apart from yeast enzyme A subunit A190. Parsimony analysis at the gene and protein levels suggests the existence of a transient ancestor to eukaryotic RNA polymerases B and C. These results are discussed in the light of the recent finding of class C genes containing RNA polymerase B promoter elements.
Amino Acid Sequence↗
Species specificity of bacterial palindromic units.
We described previously a family of dispersed palindromic sequences highly repeated in Escherichia coli and Salmonella typhimurium genomes. These sequences, called PU (palindromic units), are located outside structural genes. We report here observations suggesting that PU may have a role in bacterial speciation.
Base Sequence↗
Matching relational patterns in nucleic acid sequences.
We describe a program that efficiently searches sequence data banks for complex patterns where sites are linked by common relations such as identity, complementarity or span. Its algorithm is closer to those of automatic demonstration than to the finite state machines used in fast pattern matching. The repertory of relations can be enriched at will without rewriting the core of the program. The program is written in Pascal-ISO and runs on a microcomputer.
Base Sequence↗
Repetitive palindromic sequences in Escherichia coli. Detection and characterization with a new computer program.
We have made use of a new computer program which rapidly searches for DNA patterns irrespective of the exact sequence, in order to search systematically for repetitive palindromic structures on the Escherichia coli chromosome. By using a relatively restrictive criterion, we detected three families of palindromic structures. One is present in ribosomal RNA operons. Since seven identical ribosomal RNA operons are found on the E. coli genome, this constitutes a validation of the method. Another family is constituted by the extragenic palindromic units (PUs or REP) already described (Gilson et al., 1984). We propose a slightly different consensus for this highly repetitive and dispersed family. The last is a subclass of symmetrical transcription termination sites which we have identified. They are present in four attenuator sites and at least one terminator for convergent operons. We suggest that these symmetrical terminator sites may play a general role in the termination of transcription for convergent operons. We discuss briefly how this type of approach could be used to analyse the structure of genomes.
Algorithms↗
Molecular characterization of the resolvase gene, res, carried by a multicopy plasmid from Clostridium perfringens: common evolutionary origin for prokaryotic site-specific recombinases.
Clostridium perfringens strain CPN50 harbours a 10.2 kb plasmid known as pIP404 which, in addition to a set of UV-inducible genes involved in bacteriocin production, carries res, a gene probably encoding a site-specific recombinase. The RES protein is highly homologous to the resolvases of transposons from both Gram-negative and Gram-positive bacteria as well as enzymes involved in site-specific DNA inversion. A likely role for the RES protein would be to stabilize pIP404 by reducing the number of plasmid multimers resulting from homologous recombination. A putative resolution site for RES action was found overlapping the res promoter. Phylogenetic analysis of the primary structures of ten site-specific recombinases suggested a common descent and showed the RES protein to be closest to the resolvase encoded by Tn917 from Streptococcus faecalis.
Amino Acid Sequence↗
A simple model relevant to toxoplasmosis applied to epidemiologic results in France.
A simple mathematical model was applied to the results of a seroepidemiologic study of toxoplasmosis carried out in France in 1982-1983. An adequate fitting to the prevalence data observed on 7,605 women of childbearing age was obtained. Thus, the data were used to estimate the seroconversion rate, allowing the approach to and discussion of insights gained from the model, such as the risk of Toxoplasma infection during pregnancy, the age-related expected risks of maternal seroconversion, as well as an overall prediction of the yearly number of congenitally infected infants in the total population. In addition, the high prevalence of congenital toxoplasmosis in France and the excess risk encountered by young migrant women from lower prevalence areas were confirmed by the model. The model might therefore be useful for public health purposes in other countries.
Adolescent↗
[Comparison of several protein sequences by recognition of conserved regions].
The sequences of related proteins show the alternance of conserved and variable regions. This fact is generally seen as a reverberation of 3 D constraints onto 1 D structures. Although the exact meaning of such constraints remains elusive, conserved regions can be extracted from protein chains and used to align them. We developed a program that efficiently performs this task. The program constructs symbolic motifs fitting a target subsequence present in every chain without requiring any insertion or deletion. However, a motif can be obliterated by substitutions when it is found in a sequence. The motifs formally consist in aminoacid symbols separated (and virtually preceded and followed) by a variable number of wild-card symbols. A wild-card, which can match any aminoacid of the chains (with no increment of score), represents a variable site within conserved regions. Different motifs are progressively built by substituting a wild-card with an aminoacid symbol within or beside preexisting motifs. Only those motifs showing an outstanding association of high matching score over all chains, and of low deviation between extreme scores over individual chains are selected for making the next generation. Starting with a null motif, the construction ends when no new aminoacid can be introduced into the current motifs. A surviving motif is then considered valid if it maps without ambiguity a unique region in every sequence, and the motif with highest score is finally selected. The construction of new motifs is then reinitated for the left and right parts of the sequences, after these have been split by the previously selected motif.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
[Extraction of symbolic determinants common to a family of biological sequences].
A set of sequences can be defined by their common subsequences, and the length of these is a measure of the overall resemblance of the set. Each subsequence corresponds to a succession of symbols embedded in every sequence, following the same order but not necessarily contiguous. Determining the longest common subsequence (LCS) requires the exhaustive testing of all possible common subsequences, which sum up to about 2L, if L is the length of the shortest sequence. We present a polynomial algorithm (O(n X L4), where n is the number of sequences) for generating strings related to the LCS and constructed with the sequence alphabet and an indetermination symbol. Such strings are iteratively improved by deleting indetermination symbols and concomitantly introducing the greatest number of alphabet symbols. Processed accordingly, nucleic acid and protein sequences lead to key-words encompassing the salient positions of homologous chains, which can be used for aligning or classifying them, as well as for finding related sequences in data banks.
Amino Acid Sequence↗
Sequences of the malE gene and of its product, the maltose-binding protein of Escherichia coli K12.
The sequences of the malE gene and of its mature product, the maltose-binding protein, have been determined and are in good agreement. The malE gene encodes the pre-protein (396 amino acid residues) which yields, upon cleavage of the NH2-terminal extension (26 amino acid residues), the mature maltose-binding protein (370 amino acid residues). The malE mRNA could form stable stem and loop structures, some of which may account for translational pauses observed by Randall et al. (Randall, L., Josefsson, L. G. & Hardy, S. J. S. (1980) Eur. J. Biochem. 107, 375-379). The sequence change due to an in-frame nonpolar deletion of 765 nucleotides in malE is also presented as well as homologies between the maltose-binding protein and other sugar-binding proteins.
ATP-Binding Cassette Transporters↗
Progress in the identification of interaction sites on the periplasmic maltose binding protein from E coli.
The periplasmic maltose binding protein (MBP) is required for the high affinity transport of maltose and maltodextrins and for chemotaxis towards these sugars. In these functions, MBP interacts with proteins of the cytoplasmic membrane: MalF and MalG for transport, Tar for chemotaxis. A large number of MBP mutations have been isolated by us and other laboratories. We grouped these mutations into classes depending on the interactions affected and we represented the corresponding residues on the 3-D model for MBP so as to further identify the sites of MBP interacting with the MalF-MalG complex and with the Tar protein. MBP (like the other binding proteins) is composed of 2 lobes enclosing a cleft where the substrate binds. The face of the protein opposite the cleft seems to interact neither with MalF-MalG nor with Tar. The other face, corresponding to the cleft, contains sites for interactions with MalF-MalG and Tar. These sites appear to cover both sides of the cleft and may overlap in part. The present definition of the interaction sites suggests further that MBP has different in vivo orientations when it interacts with MalF-MalG or with Tar. This work constitutes an additional step in combining the use of genetic and structural analysis to define the interaction sites on MBP. Because of the structural similarities between periplasmic binding proteins, the regions of interaction defined could be relevant for other members of this family.
ATP-Binding Cassette Transporters↗
The maltoporin of Salmonella typhimurium: sequence and folding model.
The sequence of the lamB gene from Salmonella typhimurium was determined. It encodes the precursor to the LamB protein from S. typhimurium (pre-LamBS.t.; 452 residues) which presents extensive homologies with the pre-LamB protein from Escherichia coli (pre-LamBE.c.; 446 residues). The first third of pre-LamBS.t. is the most conserved, with 4% changes and strict identity between the signal peptides. The last two-third contains five "variable" segments where more than 50% of the residues are changed with respect to LamBE.c.. The three first variable segments are 8 to 14 residues long and contain only substitutions, while the two more distal ones are 24 and 29 residues long and also include insertions and deletions. It is remarkable that the variable segments correspond essentially to regions predicted to be extramembranous loops on our 2D folding model for LamBE.c.; they alternate with conserved predicted transmembranous segments. Four of the variable regions were predicted to be cell-surface-exposed loops on the basis of genetic and immunological data, while one of them (region II) was predicted to be periplasmic on the sole basis of folding rules. The LamB protein from S. typhimurium can substitute for the LamB protein from E. coli for maltodextrins binding and transport, but not for infection by any of the known E. coli phages using LamBE.c. for adsorption. A tetrapeptide, RGDS, assumed to be responsible for mammalian cell aggregation by LamBE.c. is conserved in LamBS.t., suggesting that it could have a functional role. The conservation of the binding and transport activity can be accounted for by the conservation of the regions known to be directly involved, namely the first third of the protein and a region corresponding to 352 to 374 of LamBS.t.. The phage resistance can be attributed to the variability of the four cell-surface-exposed loops previously identified as essential for phage adsorption. These results, together with those obtained with polyclonal and monoclonal antibodies directed against known LamB regions, strongly support the folding model presented for LamBE.c. and the idea that it can essentially be extended to LamBS.t., except perhaps for a region between residues 155 and 245. We propose that the existence of variable regions is due essentially, and perhaps only, to the local lack of structural constraints in the protein. The intergenic region between lamB and the following gene, malM, comprises conserved segments, including one palindromic unit.
Amino Acid Sequence↗
The BIME family of bacterial highly repetitive sequences.
Palindromic units (PU or REP) were initially defined as a DNA sequence of 40 nucleotides which is highly repeated in the genome of several enterobacteria and found in clusters of up to six copies. It appears now that PU belong to a larger repeated DNA element, of up to 300 nucleotides, called BIME for bacterial interspersed mosaic element. BIME is a mosaic combination of ten small DNA motifs, including the PU sequence. A central question concerning BIME is to determine whether they play a critical role within the cell. BIME exhibit only limited effects on local gene expression; it seems unlikely that these weak effects alone can account for the high BIME sequence homogeneity. It has recently been shown that DNA gyrase and DNA polymerase I are able to specifically recognize BIME DNA in vitro. These findings suggest that BIME could play a role in the functional organization of the bacterial nucleoid. Hypotheses on their origin and evolution are discussed.
Base Sequence↗