Dynamical characterization of two differentially disease associated MHC class I proteins in complex with viral and self-peptides - PubMed (original) (raw)
. 2012 Jan 13;415(2):429-42.
doi: 10.1016/j.jmb.2011.11.021. Epub 2011 Nov 16.
Affiliations
- PMID: 22119720
- DOI: 10.1016/j.jmb.2011.11.021
Dynamical characterization of two differentially disease associated MHC class I proteins in complex with viral and self-peptides
Daniele Narzi et al. J Mol Biol. 2012.
Abstract
Major histocompatibility complex (MHC) class I proteins are expressed on the cell surface where they present foreign and self-peptides to effector cells of the immune system. While an understanding of the structural prerequisites for antigen presentation has already been achieved, insight into subtype- or peptide-dependent dynamical characteristics of a peptide-MHC antigen is so far largely obscure. We approached this problem by employing 400-ns molecular dynamics simulations with two human MHC class I subtypes as model systems: the ankylosing spondylitis-associated HLA-B∗27:05 and the non-ankylosing spondylitis-associated HLA-B∗27:09. Both proteins differ only by a micropolymorphism at the floor of the peptide binding groove (Asp116His). A viral (pLMP2) and three self-peptides (pVIPR, pGR, and TIS) were evaluated. The stability of the binding grooves was found to be both subtype dependent and peptide dependent. A detachment from the C- and/or N-terminal pockets was observed for all peptides except TIS, resulting in a stabilization of the α1-helix in both TIS-displaying subtypes. Estimates of the entropy associated with the bound peptides showed an increased entropy for pLMP2 presented by B∗27:05 as compared to B∗27:09, in contrast to the self-peptides. Additionally, the flexibility of the α1-helix that is probably important for receptor binding to the B27:peptide epitope is significantly enhanced for B∗27:05. These in silico results show that the dynamic properties of peptide-MHC complexes are affected both by the bound peptide and by micropolymorphisms of the heavy chain. Our findings suggest a role for the conformational flexibility of MHC class I molecules in the context of recognition by receptors on effector cells.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Similar articles
- HLA-B27 heavy chains distinguished by a micropolymorphism exhibit differential flexibility.
Fabian H, Huser H, Loll B, Ziegler A, Naumann D, Uchanska-Ziegler B. Fabian H, et al. Arthritis Rheum. 2010 Apr;62(4):978-87. doi: 10.1002/art.27316. Arthritis Rheum. 2010. PMID: 20131248 - HLA-B27 subtypes differentially associated with disease exhibit conformational differences in solution.
Fabian H, Huser H, Narzi D, Misselwitz R, Loll B, Ziegler A, Böckmann RA, Uchanska-Ziegler B, Naumann D. Fabian H, et al. J Mol Biol. 2008 Feb 22;376(3):798-810. doi: 10.1016/j.jmb.2007.12.009. Epub 2007 Dec 8. J Mol Biol. 2008. PMID: 18178223 - Thermodynamic and structural equivalence of two HLA-B27 subtypes complexed with a self-peptide.
Hülsmeyer M, Welfle K, Pöhlmann T, Misselwitz R, Alexiev U, Welfle H, Saenger W, Uchanska-Ziegler B, Ziegler A. Hülsmeyer M, et al. J Mol Biol. 2005 Mar 11;346(5):1367-79. doi: 10.1016/j.jmb.2004.12.047. Epub 2005 Jan 28. J Mol Biol. 2005. PMID: 15713487 - HLA class I-associated diseases with a suspected autoimmune etiology: HLA-B27 subtypes as a model system.
Uchanska-Ziegler B, Loll B, Fabian H, Hee CS, Saenger W, Ziegler A. Uchanska-Ziegler B, et al. Eur J Cell Biol. 2012 Apr;91(4):274-86. doi: 10.1016/j.ejcb.2011.03.003. Epub 2011 Jun 12. Eur J Cell Biol. 2012. PMID: 21665321 Review. - Presentation of a self-peptide in two distinct conformations by a disease-associated HLA-B27 subtype.
Wucherpfennig KW. Wucherpfennig KW. J Exp Med. 2004 Jan 19;199(2):151-4. doi: 10.1084/jem.20032050. J Exp Med. 2004. PMID: 14734520 Free PMC article. Review. No abstract available.
Cited by
- MHC-Fine: Fine-tuned AlphaFold for precise MHC-peptide complex prediction.
Glukhov E, Kalitin D, Stepanenko D, Zhu Y, Nguyen T, Jones G, Patsahan T, Simmerling C, Mitchell JC, Vajda S, Dill KA, Padhorny D, Kozakov D. Glukhov E, et al. Biophys J. 2024 Sep 3;123(17):2902-2909. doi: 10.1016/j.bpj.2024.05.011. Epub 2024 May 15. Biophys J. 2024. PMID: 38751115 - MHC-Fine: Fine-tuned AlphaFold for Precise MHC-Peptide Complex Prediction.
Glukhov E, Kalitin D, Stepanenko D, Zhu Y, Nguyen T, Jones G, Simmerling C, Mitchell JC, Vajda S, Dill KA, Padhorny D, Kozakov D. Glukhov E, et al. bioRxiv [Preprint]. 2023 Dec 14:2023.11.29.569310. doi: 10.1101/2023.11.29.569310. bioRxiv. 2023. PMID: 38077000 Free PMC article. Updated. Preprint. - Fast peptide exchange on major histocompatibility complex class I molecules by acidic stabilization of a peptide-empty intermediate.
Saikia A, Hadeler A, Prasad P, Zacharias M, Springer S. Saikia A, et al. Protein Sci. 2022 Dec;31(12):e4478. doi: 10.1002/pro.4478. Protein Sci. 2022. PMID: 36258668 Free PMC article. - Charge-based interactions through peptide position 4 drive diversity of antigen presentation by human leukocyte antigen class I molecules.
Jackson KR, Antunes DA, Talukder AH, Maleki AR, Amagai K, Salmon A, Katailiha AS, Chiu Y, Fasoulis R, Rigo MM, Abella JR, Melendez BD, Li F, Sun Y, Sonnemann HM, Belousov V, Frenkel F, Justesen S, Makaju A, Liu Y, Horn D, Lopez-Ferrer D, Huhmer AF, Hwu P, Roszik J, Hawke D, Kavraki LE, Lizée G. Jackson KR, et al. PNAS Nexus. 2022 Jul 27;1(3):pgac124. doi: 10.1093/pnasnexus/pgac124. eCollection 2022 Jul. PNAS Nexus. 2022. PMID: 36003074 Free PMC article. - Conformational flexibility of a free and TCR-bound pMHC-I protein investigated by long-term molecular dynamics simulations.
Tomasiak L, Karch R, Schreiner W. Tomasiak L, et al. BMC Immunol. 2022 Jul 29;23(Suppl 1):36. doi: 10.1186/s12865-022-00510-7. BMC Immunol. 2022. PMID: 35902791 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous