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Helical Propensity (helical + propensity)
Selected AbstractsHelix-coil energetics for helix formers and breakers reflect context and temperature: Mutants of helically robust, guest-sensitive homopeptide hostsBIOPOLYMERS, Issue 5 2009Khaled A. Nasr Abstract The natural amino acids are primarily helix breakers at the low assignment temperatures characteristic of many studies, but recent genomic analyses of thermophilic proteins suggest that at high temperatures, some breakers may become strong helix formers. Moreover, the breaker/former inventory has not been previously characterized at the physiologically relevant temperature of 37°C. The versatility of 13CO NMR chemical shifts as helicity reporters allows construction of two mutant peptide series, tailored to expand the range of temperature assignments for helical propensities and derived from the core hosts tL-Ala9XxxAla9 - tL and tL-AlaNva4XxxNva4Ala9 - tL, Nva = norvaline. For three limiting guests Xxx, the helix former Nva and the breakers Gly and Pro, we report wXxx[T] assignments at seven temperatures from 2 to 80°C, validating our reasoning and paving the way for assignment of a definitive wXxx[T] data-base. © 2008 Wiley Periodicals, Inc. Biopolymers 91: 311,320, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Probing the ,-Helical Structural Stability of Stapled p53 Peptides: Molecular Dynamics Simulations and AnalysisCHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2010Zuojun Guo Reactivation of the p53 cell apoptosis pathway through inhibition of the p53-hDM2 interaction is a viable approach to suppress tumor growth in many human cancers and stabilization of the helical structure of synthetic p53 analogs via a hydrocarbon cross-link (staple) has been found to lead to increased potency and inhibition of protein,protein binding (J. Am. Chem. Soc. 129: 5298). However, details of the structure and dynamic stability of the stapled peptides are not well understood. Here, we use extensive all-atom molecular dynamics simulations to study a series of stapled ,-helical peptides over a range of temperatures in solution. The peptides are found to exhibit substantial variations in predicted ,-helical propensities that are in good agreement with the experimental observations. In addition, we find significant variation in local structural flexibility of the peptides with the position of the linker, which appears to be more closely related to the observed differences in activity than the absolute ,-helical stability. These simulations provide new insights into the design of ,-helical stapled peptides and the development of potent inhibitors of ,-helical protein,protein interfaces. [source] Do Valine Side Chains Have an Influence on the Folding Behavior of , -Substituted , -Peptides?HELVETICA CHIMICA ACTA, Issue 10 2004Alice Glättli The influence of valine side chains on the folding/unfolding equilibrium and, in particular, on the 314 -helical propensity of ,3 -peptides were investigated by means of molecular-dynamics (MD) simulation. To that end, the valine side chains in two different ,3 -peptides were substituted by leucine side chains. The resulting four peptides, of which three have never been synthesized, were simulated for 150 to 200,ns at 298 and 340,K, starting from a fully extended conformation. The simulation trajectories obtained were compared with respect to structural preferences and folding behavior. All four peptides showed a similar folding behavior and were found to predominantly adopt 314 -helical conformations, irrespective of the presence of valine side chains. No other well-defined conformation was observed at significant population in any of the simulations. Our results imply that ,3 -peptides show a structural preference for 314 -helices independent of the branching nature of the side chains, in contrast to what has been previously proposed on the basis of circular-dichroism (CD) measurements. [source] Sensitivity of secondary structure propensities to sequence differences between ,- and ,-synuclein: Implications for fibrillationPROTEIN SCIENCE, Issue 12 2006Joseph A. Marsh Abstract The synucleins are a family of intrinsically disordered proteins involved in various human diseases. ,-Synuclein has been extensively characterized due to its role in Parkinson's disease where it forms intracellular aggregates, while ,-synuclein is overexpressed in a majority of late-stage breast cancers. Despite fairly strong sequence similarity between the amyloid-forming regions of ,- and ,-synuclein, ,-synuclein has only a weak propensity to form amyloid fibrils. We hypothesize that the different fibrillation tendencies of ,- and ,-synuclein may be related to differences in structural propensities. Here we have measured chemical shifts for ,-synuclein and compared them to previously published shifts for ,-synuclein. In order to facilitate direct comparison, we have implemented a simple new technique for re-referencing chemical shifts that we have found to be highly effective for both disordered and folded proteins. In addition, we have developed a new method that combines different chemical shifts into a single residue-specific secondary structure propensity (SSP) score. We observe significant differences between ,- and ,-synuclein secondary structure propensities. Most interestingly, ,-synuclein has an increased ,-helical propensity in the amyloid-forming region that is critical for ,-synuclein fibrillation, suggesting that increased structural stability in this region may protect against ,-synuclein aggregation. This comparison of residue-specific secondary structure propensities between intrinsically disordered homologs highlights the sensitivity of transient structure to sequence changes, which we suggest may have been exploited as an evolutionary mechanism for fast modulation of protein structure and, hence, function. [source] A statistically derived parameterization for the collagen triple-helixPROTEIN SCIENCE, Issue 11 2002Jan K. Rainey Abstract The triple-helix is a unique secondary structural motif found primarily within the collagens. In collagen, it is a homo- or hetero-tripeptide with a repeating primary sequence of (Gly-X-Y)n, displaying characteristic peptide backbone dihedral angles. Studies of bulk collagen fibrils indicate that the triple-helix must be a highly repetitive secondary structure, with very specific constraints. Primary sequence analysis shows that most collagen molecules are primarily triple-helical; however, no high-resolution structure of any entire protein is yet available. Given the drastic morphological differences in self-assembled collagen structures with subtle changes in assembly conditions, a detailed knowledge of the relative locations of charged and sterically bulky residues in collagen is desirable. Its repetitive primary sequence and highly conserved secondary structure make collagen, and the triple-helix in general, an ideal candidate for a general parameterization for prediction of residue locations and for the use of a helical wheel in the prediction of residue orientation. Herein, a statistical analysis of the currently available high-resolution X-ray crystal structures of model triple-helical peptides is performed to produce an experimentally based parameter set for predicting peptide backbone and C, atom locations for the triple-helix. Unlike existing homology models, this allows easy prediction of an entire triple-helix structure based on all existing high-resolution triple-helix structures, rather than only on a single structure or on idealized parameters. Furthermore, regional differences based on the helical propensity of residues may be readily incorporated. The parameter set is validated in terms of the predicted bond lengths, backbone dihedral angles, and interchain hydrogen bonding. [source] Control of helix sense in protein-mimicking backbone by the noncovalent chiral effectTHE CHEMICAL RECORD, Issue 3 2007Yoshihito Inai Abstract We have reviewed our previous work regarding induction or control of a peptide helix sense through chiral stimulus to the peptide chain terminus. An optically inactive 310 -helix designed mainly with unusual ,-amino acid residues was commonly employed. Such an N-terminal-free peptide generates a preferred helix sense by chiral acid molecule. A helix sense pre-directed in chiral sequence is also influenced or controlled by the chiral sign of such external molecule. Here free amide groups in the 310 -helical N-terminus participate in the formation of a multipoint coordinated complex. The terminal asymmetry produces the noncovalent chiral domino effect (NCDE) to influence the whole helix sense. The NCDE-mediated control of helicity provides the underlying chiral nature of protein-mimicking helical backbones: notably, chiral recognition at the terminus and modulation of helical propensity through chiral stimulus. The above items from our previous reports have been outlined and reviewed together with their significance in biopolymer science and chiral chemistry. © 2007 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 7: 191,202; 2007: Published online in Wiley Inter-Science (www.interscience.wiley.com) DOI 10.1002/tcr.20116 [source] The N-terminal region of Pseudomonas type III effector AvrPtoB elicits Pto-dependent immunity and has two distinct virulence determinantsTHE PLANT JOURNAL, Issue 4 2007Fangming Xiao Summary Resistance to bacterial speck disease in tomato is activated by the physical interaction of the host Pto kinase with either of the sequence-dissimilar type III effector proteins AvrPto or AvrPtoB (HopAB2) from Pseudomonas syringae pv. tomato. Pto-mediated immunity requires Prf, a protein with a nucleotide-binding site and leucine-rich repeats. The N-terminal 307 amino acids of AvrPtoB were previously reported to interact with the Pto kinase, and we show here that this region (AvrPtoB1-307) is sufficient for eliciting Pto/Prf-dependent immunity against P. s. pv. tomato. AvrPtoB1-307 was also found to be sufficient for a virulence activity that enhances ethylene production and increases growth of P. s. pv. tomato and severity of speck disease on susceptible tomato lines lacking either Pto or Prf. Moreover, we found that residues 308,387 of AvrPtoB are required for the previously reported ability of AvrPtoB to suppress pathogen-associated molecular patterns-induced basal defenses in Arabidopsis. Thus, the N-terminal region of AvrPtoB has two structurally distinct domains involved in different virulence-promoting mechanisms. Random and targeted mutagenesis identified five tightly clustered residues in AvrPtoB1-307 that are required for interaction with Pto and for elicitation of immunity to P. s. pv. tomato. Mutation of one of the five clustered residues abolished the ethylene-associated virulence activity of AvrPtoB1-307. However, individual mutations of the other four residues, despite abolishing interaction with Pto and avirulence activity, had no effect on AvrPtoB1-307 virulence activity. None of these mutations affected the basal defense-suppressing activity of AvrPtoB1-387. Based on sequence alignments, estimates of helical propensity, and the previously reported structure of AvrPto, we hypothesize that the Pto-interacting domains of AvrPto and AvrPtoB1-307 have structural similarity. Together, these data support a model in which AvrPtoB1-307 promotes ethylene-associated virulence by interaction not with Pto but with another unknown host protein. [source] | |||||||||||||