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At least 199 records · Page 11Linked to original sources
PubMed2005

The NMR and X-ray structures of the Saccharomyces cerevisiae Vts1 SAM domain define a surface for the recognition of RNA hairpins.

The SAM domain of the Saccharomyces cerevisiae post-transcriptional regulator Vts1 has a high affinity towards RNA hairpins containing a CUGGC pentaloop. We present the 1.6 Angstroms X-ray crystal structure of the Vts1 SAM domain in its unliganded state, and the NMR solution structure of this domain in its RNA-bound state. Both structures reveal a canonical five helix SAM domain flanked by additional secondary structural elements at the N and C termini. The two structures are essentially identical, implying that no major structural rearrangements occur upon RNA binding. Amide chemical shift changes map the RNA-binding site to a shallow, basic patch at the junction of helix alpha5 and the loop connecting helices alpha1 and alpha2.

Crystallography, X-Ray↗
PubMed2006

Magnetoencephalographic analysis of cortical oscillatory activity in patients with brain tumors: Synthetic aperture magnetometry (SAM) functional imaging of delta band activity.

Abnormal focal slow wave activity on electroencephalography and magnetoencephalography (MEG) is often seen in patients with various brain pathologies and MEG is capable of localizing cortical oscillatory activity with enhanced accuracy. In addition, MEG with synthetic aperture magnetometry (SAM) can depict changes in cortical oscillatory activity tomographically. Using SAM, we recorded cortical rhythms in patients with a brain tumor and evaluated the tomographic appearance of focal slow wave activity in relation to clinical signs and symptoms. Spontaneous MEG recordings were obtained in 15 patients with brain tumors. Statistically-determined power distributions in the delta-, theta-, and alpha-frequency bands were displayed tomographically and overlaid on individual magnetic resonance images. The location, strength and volume of enhanced activity were analyzed. Delta and theta band activities were significantly more intense in the cortex adjacent to tumors and in the surrounding edematous cortical areas than in other portions of the cortex. In 13 of the 15 patients, spatial distribution of enhanced focal delta activity coincided with the area responsible for the presenting signs and symptoms. Volumetric analysis revealed that emergence of tumor-related focal delta band activity in the cortex adjacent to a tumor, or with peritumoral edema, was greater for intra-axial tumors involving subcortical fibers than for extra-axial tumors. Patients with an increased volume of enhanced delta activity exhibited poor recovery of function in the early postoperative period. It is concluded that SAM imaging of focal delta activity can reveal functional alterations in cortical activity in patients with brain tumors and is useful for assessing cortical states associated with the existing pathology.

Adult↗
PubMed2003

SAM domains: uniform structure, diversity of function.

Sterile alpha motif (SAM) domains are known to exhibit diverse protein-protein interaction modes. They can form multiple self-association architectures and also bind to various non-SAM domain-containing proteins. Surprising new work adds a completely unanticipated function for some SAM domains - the ability to bind RNA. Such functional diversity within a homologous protein family presents a significant challenge for bioinformatic function assignment.

Binding Sites↗
PubMedDate not supplied

Senescence-accelerated mouse (SAM): a biogerontological resource in aging research.

The senescence-accelerated mouse (SAM), consisting of 14 senescence-prone inbred strains (SAMP) and 4 senescence-resistant inbred strains (SAMR) has been under development since 1970 through the selective inbreeding of AKR/J strain mice donated by the Jackson laboratory in 1968, based on the data of the grading score of senescence, life span, and pathologic phenotypes. The characteristic feature of aging common to all SAMP and SAMR mice is accelerated senescence and normal aging, respectively. Furthermore, SAMP and SAMR strains manifest various pathobiological phenotypes which include such neurobiological phenotypes as deficits in learning and memory, emotional disorders, abnormal circadian rhythms, brain atrophy, hearing impairment, etc., and are often characteristic enough to differentiate the strains. Various efforts are currently being made using the SAM model to clarify the underlying mechanisms in accelerated senescence as well as the etiopathogenic mechanisms in age-associated pathobiologies. Genetic background and significance of SAM development are discussed.

Aging↗
PubMedDate not supplied

Genetic characterization of senescence-accelerated mouse (SAM).

The Senescence-Accelerated Mouse (SAM) strains are unique and appropriate models for genetic studies on aging because the SAMP strains have an "accelerated senescence" phenotype for which the SAMR strains are controls, and each SAMP strain has a strain-specific age-associated disorder. Furthermore, because they have gone through sufficient generations of sister-brother mating, they can be considered inbred strains, which can be analyzed genetically. There are now 11 SAMP strains and 3 SAMR strains descended from the progenitor litters. Analysis with the Gompertz function shows that the SAMP strains have the same initial mortality rate (IMR) as the SAMR strains but a shorter mortality rate doubling time (MRDT), presumably due to genes that accelerated the rate of senescence in the SAMP strains. This accelerated senescence may also occur in cultured fibroblast-like cells. We performed molecular genetic characterization of all the SAM strains to acquire a base of genetic information from which we could develop hypotheses on the mechanism of development of SAM strains and genetic factors that contribute to accelerated senescence.

Aging↗
PubMed2003

RNA recognition via the SAM domain of Smaug.

The Nanos protein gradient in Drosophila, required for proper abdominal segmentation, is generated in part via translational repression of its mRNA by Smaug. We report here the crystal structure of the Smaug RNA binding domain, which shows no sequence homology to any previously characterized RNA binding motif. The structure reveals an unusual makeup in which a SAM domain, a common protein-protein interaction module, is affixed to a pseudo-HEAT repeat analogous topology (PHAT) domain. Unexpectedly, we find through a combination of structural and genetic analysis that it is primarily the SAM domain that interacts specifically with the appropriate nanos mRNA regulatory sequence. Therefore, in addition to their previously characterized roles in protein-protein interactions, some SAM domains play crucial roles in RNA binding.

Amino Acid Sequence↗
PubMed2002

Equilibrium unfolding of the C-terminal SAM domain of p73.

The sterile alpha motif (SAM) domain is a protein module of approximately 65 to 70 amino acids found in many diverse proteins whose functions range from signal transduction to transcriptional repression. The alpha splice variant of p73 (p73 alpha), a homologue of the tumor suppressor p53, has close to its C-terminus a SAM motif. Here, we report the folding equilibrium properties of the p73 alpha SAM domain (SAMp73) by using different biophysical techniques (circular dichroism, fluorescence, and Fourier transform infrared spectroscopies, and differential scanning calorimetry). Those probes indicate that SAMp73 folds via a two-state mechanism. Fluorescence experiments performed at different pHs showed two titrations: the first one due to an acid residue (with a pK(a) = 4.5 +/- 0.3) and the second due to deprotonation of tyrosine residues. The conformational stability of the protein upon chemical denaturation was determined over the pH range 3 to 10. The maximum conformational stability is DeltaG = 5.7 +/- 0.4 kcal x mol(-1) (at 25 degrees C) and occurs in a broad maximum, with little variation, between pH 6 and 10. The high melting temperature of SAMp73 (T(m) = 93.5 degrees C), despite its moderate conformational stability at 25 degrees C, can be ascribed to its low heat capacity change upon unfolding, DeltaC(p), which is estimated to be around 915 cal x K(-1) x mol(-1) at 25 degrees C and only around 543 cal x K(-1) x mol(-1) at the T(m). The implications of the temperature-dependent nature of DeltaC(p) are discussed in relation to the thermal stability of proteins as opposed to their conformational stability at room temperature.

Amino Acid Motifs↗
PubMed2005

Local packing environment strongly influences the frictional properties of mixed CH3- and CF3-terminated alkanethiol SAMs on Au(111).

Compositionally mixed, self-assembled monolayers (SAMs) derived from 16,16,16-trifluorohexadecanethiol and a normal alkanethiol, either hexadecanethiol or pentadecanethiol, were formed on Au(111) substrates. The relative composition of the films was determined using X-ray photoelectron spectroscopy and was found to approximately equal the equimolar composition of the isooctane solution from which they were formed. The frictional properties of the mixed films were measured on the nanometer scale using atomic force microscopy and were observed to decrease when the chain length of the CH(3)-terminated component was shortened by one methylene unit (i.e., when hexadecanethiol was replaced by pentadecanethiol). For comparison, the frictional properties of a mixed-chain-length CH(3)-terminated SAM derived from hexadecanethiol and pentadecanethiol in a 1:1 ratio was also examined. In contrast to the mixed CF(3)/CH(3) system, the latter mixed-chain-length system exhibited relatively higher friction when compared to single-component SAMs derived solely from either hexadecanethiol or pentadecanethiol. For both types of mixed films, the change in frictional properties that occurs as a result of modifying the position of neighboring terminal groups with respect to the surface plane is discussed in terms of the influence of local packing environments on interfacial energy dissipation (friction).

Journal Article↗
PubMed2006

Deposition of DNA rafts on cationic SAMs on silicon [100].

We demonstrate a guided self-assembly approach to the fabrication of DNA nanostructures on silicon substrates. DNA oligonucleotides self-assemble into "rafts" 8 x 37 x 2 nm in size. The rafts bind to cationic SAMs on silicon wafers. Electron-beam lithography of a thin poly(methyl methacrylate) (PMMA) resist layer was used to define trenches, and (3-aminopropyl)triethoxysilane (APTES), a cationic SAM precursor, was deposited from aqueous solution onto the exposed silicon dioxide at the trench bottoms. The remaining PMMA can be cleanly stripped off with dichloromethane, leaving APTES layers 0.7-1.2 nm in thickness and 110 nm in width. DNA rafts bind selectively to the resulting APTES stripes. The coverage of DNA rafts on adjacent areas of silicon dioxide is 20 times lower than on the APTES stripes. The topographic features of the rafts, measured by AFM, are identical to those of rafts deposited on wide-area SAMs. Binding to the APTES stripes appears to be very strong as indicated by "jamming" of the rafts at a saturation coverage of 42% and the stability to repeated AFM scanning in air.

Microscopy, Atomic Force↗
PubMed2006

Fabrication of flexible gold films with periodic sub-micrometer roughness and their wettability control by modification of SAM.

Flexible honeycomb gold films supported by polymer sheets are fabricated by using polystyrene particle monolayers. The surfaces of the flexible gold films are covered with self-assembled monolayers (SAMs) of hydrophobic or hydrophilic thiol compounds, and the wettability of the modified surface is evaluated by measurements of the contact angles of water droplets. The contact angle of the film covered with hydrophobic SAM is ca. 150 degrees, which is greater than the value of 112 degrees for a flat gold surface, while the values for hydrophilic SAM are below 10 degrees.

Journal Article↗
PubMed1997

Effect of "beta CATECHIN" on the life span of senescence accelerated mice (SAM-P8 strain).

"beta CATECHIN", a preparation of natural vitamins and phytosubstances, has been designed as an "universal antioxidant' drink. Having previously demonstrated the scavenging action of a variety of free radicals by "beta CATECHIN", we now report the effect of its long term administration on the life span of senesescence accelerated mice (SAM-P8), a murine model system that offers many characteristics of mammalian aging with a shortened life span. Both male and female SAM (age: 10 weeks) maintained on "beta CATECHIN" containing drinking water (1ml/kg b.w) showed significant extension of the mean life span as compared to their respective controls that received normal drinking water. Results show that administration of "beta CATECHIN" increased the 50% mean survival rate by 8 weeks in case of female, and 7.5 weeks for male SAM. In addition to offering fresh evidence to the "free radical theory of aging", the results emphasize on the importance of a daily supplement of natural antioxidants, especially as a combination, to achieve the goal of a long and disease-free life.

Aging↗
PubMed2002

Diacylglycerol kinase delta suppresses ER-to-Golgi traffic via its SAM and PH domains.

We report here that the anterograde transport from the endoplasmic reticulum (ER) to the Golgi was markedly suppressed by diacylglycerol kinase delta (DGKdelta) that uniquely possesses a pleckstrin homology (PH) and a sterile alpha motif (SAM) domain. A low-level expression of DGKdelta in NIH3T3 cells caused redistribution into the ER of the marker proteins of the Golgi membranes and the vesicular-tubular clusters (VTCs). In this case DGKdelta delayed the ER-to-Golgi traffic of vesicular stomatitis virus glycoprotein (VSV G) and also the reassembly of the Golgi apparatus after brefeldin A (BFA) treatment and washout. DGKdelta was demonstrated to associate with the ER through its C-terminal SAM domain acting as an ER-targeting motif. Both of the SAM domain and the N-terminal PH domain of DGKdelta were needed to exert its effects on ER-to-Golgi traffic. Kinase-dead mutants of DGKdelta were also effective as the wild-type enzyme, suggesting that the catalytic activity of DGK was not involved in the present observation. Remarkably, the expression of DGKdelta abrogated formation of COPII-coated structures labeled with Sec13p without affecting COPI structures. These findings indicate that DGKdelta negatively regulates ER-to-Golgi traffic by selectively inhibiting the formation of ER export sites without significantly affecting retrograde transport.

3T3 Cells↗
PubMed1999

Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain.

p73 and p63 are two recently cloned genes with homology to the tumor suppressor p53, whose protein product is a key transcriptional regulator of genes involved in cell cycle arrest and apoptosis. While all three proteins share conserved transcriptional activation, DNA-binding and oligomerization domains, p73 and p63 have an additional conserved C-terminal region. We have determined the three-dimensional solution structure of this conserved C-terminal domain of human p73. The structure reveals a small five-helix bundle with striking similarity to the SAM (sterile alpha motif) domains of two ephrin receptor tyrosine kinases. The SAM domain is a putative protein-protein interaction domain found in a variety of cytoplasmic signaling proteins and has been shown to form both homo- and hetero-oligomers. However, the SAM-like C-terminal domains of p73 and p63 are monomeric and do not interact with one another, suggesting that this domain may interact with additional, as yet uncharacterized proteins in a signaling and/or regulatory role.

Amino Acid Sequence↗
PubMed2001

Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods.

A novel protein superfamily with over 600 members was discovered by iterative profile searches and analyzed with powerful bioinformatics and information visualization methods. Evidence exists that these proteins generate a radical species by reductive cleavage of S:-adenosylmethionine (SAM) through an unusual Fe-S center. The superfamily (named here Radical SAM) provides evidence that radical-based catalysis is important in a number of previously well- studied but unresolved biochemical pathways and reflects an ancient conserved mechanistic approach to difficult chemistries. Radical SAM proteins catalyze diverse reactions, including unusual methylations, isomerization, sulfur insertion, ring formation, anaerobic oxidation and protein radical formation. They function in DNA precursor, vitamin, cofactor, antibiotic and herbicide biosynthesis and in biodegradation pathways. One eukaryotic member is interferon-inducible and is considered a candidate drug target for osteoporosis; another is observed to bind the neuronal Cdk5 activator protein. Five defining members not previously recognized as homologs are lysine 2,3-aminomutase, biotin synthase, lipoic acid synthase and the activating enzymes for pyruvate formate-lyase and anaerobic ribonucleotide reductase. Two functional predictions for unknown proteins are made based on integrating other data types such as motif, domain, operon and biochemical pathway into an organized view of similarity relationships.

Amino Acid Sequence↗
PubMed2001

Structure of the C-terminal sterile alpha-motif (SAM) domain of human p73 alpha.

p73 is a homologue of the tumour suppressor p53 and contains all three functional domains of p53. The alpha-splice variant of p73 (p73 alpha) contains near its C-terminus an additional structural domain known as the sterile alpha-motif (SAM) that is probably responsible for regulating p53-like functions of p73. Here, the 2.54 A resolution crystal structure of this protein domain is reported. The crystal structure and the published solution structure have the same five-helix bundle fold that is characteristic of all SAM-domain structures, with an overall r.m.s.d. of 1.5 A for main-chain atoms. The hydrophobic core residues are well conserved, yet some large local differences are observed. The crystal structure reveals a dimeric organization, with the interface residues forming a mini four-helix bundle. However, analysis of solvation free energies and the surface area buried upon dimer formation indicated that this arrangement is more likely to be an effect of crystal packing rather than reflecting a physiological state. This is consistent with the solution structure being a monomer. The p73 alpha SAM domain also contains several interesting structural features: a Cys-X-X-Cys motif, a 3(10)-helix and a loop that have elevated B factors, and short tight inter-helical loops including two beta-turns; these elements are probably important in the normal function of this domain.

Amino Acid Motifs↗
PubMed2005

The crystal structure of a novel SAM-dependent methyltransferase PH1915 from Pyrococcus horikoshii.

The S-adenosyl-L-methionine (SAM)-dependent methyltransferases represent a diverse and biologically important class of enzymes. These enzymes utilize the ubiquitous methyl donor SAM as a cofactor to methylate proteins, small molecules, lipids, and nucleic acids. Here we present the crystal structure of PH1915 from Pyrococcus horikoshii OT3, a predicted SAM-dependent methyltransferase. This protein belongs to the Cluster of Orthologous Group 1092, and the presented crystal structure is the first representative structure of this protein family. Based on sequence and 3D structure analysis, we have made valuable functional insights that will facilitate further studies for characterizing this group of proteins. Specifically, we propose that PH1915 and its orthologs are rRNA- or tRNA-specific methyltransferases.

Binding Sites↗
PubMed1999

p53 Family members p63 and p73 are SAM domain-containing proteins.

Homologs of the tumor suppressor p53, called p63 and p73, have been identified. The p63 and p73 family members possess a domain structure similar to p53, but contain variable C-terminal extensions. We find that some of the C-terminal extensions contain Sterile Alpha Motif (SAM) domains. SAM domains are protein modules that are involved in protein-protein interactions. Consistent with this role, the C-terminal SAM domains of the p63 and p73 may regulate function by recruiting other protein effectors.

Amino Acid Sequence↗
PubMed1999

Oligomeric structure of the human EphB2 receptor SAM domain.

The sterile alpha motif (SAM) domain is a protein interaction module that is present in diverse signal-transducing proteins. SAM domains are known to form homo- and hetero-oligomers. The crystal structure of the SAM domain from an Eph receptor tyrosine kinase, EphB2, reveals two large interfaces. In one interface, adjacent monomers exchange amino-terminal peptides that insert into a hydrophobic groove on each neighbor. A second interface is composed of the carboxyl-terminal helix and a nearby loop. A possible oligomer, constructed from a combination of these binding modes, may provide a platform for the formation of larger protein complexes.

Binding Sites↗