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• W2992322182 abstract "Abstract Class I Major Histocompatibility Complex (MHC) binds short antigenic peptides with the help of Peptide Loading Complex (PLC), and presents them to T-cell Receptors (TCRs) of cytotoxic T-cells and Killer-cell Immunglobulin-like Receptors (KIRs) of Natural Killer (NK) cells. With more than 10000 alleles, the Human Leukocyte Antigen (HLA) chain of MHC is the most polymorphic protein in humans. This allelic diversity provides a wide coverage of peptide sequence space, yet does not affect the three-dimensional structure of the complex. Moreover, TCRs mostly interact with pMHC in a common diagonal binding mode, and KIR-pMHC interaction is allele-dependent. With the aim of establishing a framework for understanding the relationships between polymorphism (sequence), structure (conserved fold) and function (protein interactions) of the MHC, we performed here a local frustration analysis on pMHC homology models covering 1436 HLA I alleles. An analysis of local frustration profiles indicated that (1) variations in MHC fold are unlikely due to minimally-frustrated and relatively conserved residues within the HLA peptide-binding groove, (2) high frustration patches on HLA helices are either involved in or near interaction sites of MHC with the TCR, KIR, or Tapasin of the PLC, and (3) peptide ligands mainly stabilize the F-pocket of HLA binding groove. Author Summary A protein complex called the Major Histocompatibility Complex (MHC) plays a critical role in our fight against pathogens via presentation of antigenic peptides to receptor molecules of our immune system cells. Our knowledge on genetics, structure and protein interactions of MHC revealed that the peptide-binding groove of Human Leukocyte Chain (HLA I) of this complex is highly polymorphic and interacts with different proteins for peptide-binding and presentation over the course of its lifetime. Although the relationship between polymorphism and peptide-binding is well-known, we still lack a proper framework to understand how this polymorphism affects the overall MHC structure and protein interactions. Here, we used computational biophysics methods to generate structural models of 1436 HLA I alleles, and quantified local frustration within the HLA I, which indicates energetic optimization levels of contacts between amino acids. We identified a group of minimally frustrated and conserved positions which may be responsible for the conserved MHC structure, and detected high frustration patches on HLA surface positions taking part in interactions with other immune system proteins. Our results provide a biophysical basis for relationships between sequence, structure, and function of MHC I." @default.
• W2992322182 created "2019-12-13" @default.
• W2992322182 creator A5040851431 @default.
• W2992322182 creator A5077817912 @default.
• W2992322182 date "2019-12-06" @default.
• W2992322182 modified "2023-09-25" @default.
• W2992322182 title "Sequence-structure-function relationships in class I MHC: a local frustration perspective" @default.
• W2992322182 cites W1141951150 @default.
• W2992322182 cites W1488104559 @default.
• W2992322182 cites W1551056911 @default.
• W2992322182 cites W1680513302 @default.
• W2992322182 cites W1755079061 @default.
• W2992322182 cites W1804480117 @default.
• W2992322182 cites W1868344454 @default.
• W2992322182 cites W1870117245 @default.
• W2992322182 cites W190768114 @default.
• W2992322182 cites W1913704715 @default.
• W2992322182 cites W1927002144 @default.
• W2992322182 cites W1963309870 @default.
• W2992322182 cites W1965294699 @default.
• W2992322182 cites W1977385060 @default.
• W2992322182 cites W1984011179 @default.
• W2992322182 cites W1985466457 @default.
• W2992322182 cites W1991194470 @default.
• W2992322182 cites W1992874693 @default.
• W2992322182 cites W1992898397 @default.
• W2992322182 cites W1995167648 @default.
• W2992322182 cites W1995875735 @default.
• W2992322182 cites W1998240361 @default.
• W2992322182 cites W2012384730 @default.
• W2992322182 cites W2013435992 @default.
• W2992322182 cites W2024991365 @default.
• W2992322182 cites W2027036222 @default.
• W2992322182 cites W2032428654 @default.
• W2992322182 cites W2038509173 @default.
• W2992322182 cites W2040783956 @default.
• W2992322182 cites W2052321000 @default.
• W2992322182 cites W2053707749 @default.
• W2992322182 cites W2054017637 @default.
• W2992322182 cites W2056384440 @default.
• W2992322182 cites W2059575487 @default.
• W2992322182 cites W2065237490 @default.
• W2992322182 cites W2072747310 @default.
• W2992322182 cites W2076455712 @default.
• W2992322182 cites W2079759605 @default.
• W2992322182 cites W2082515849 @default.
• W2992322182 cites W2088616197 @default.
• W2992322182 cites W2091335989 @default.
• W2992322182 cites W2098073190 @default.
• W2992322182 cites W2098103958 @default.
• W2992322182 cites W2099028937 @default.
• W2992322182 cites W2100139545 @default.
• W2992322182 cites W2107985990 @default.
• W2992322182 cites W2112752664 @default.
• W2992322182 cites W2113551702 @default.
• W2992322182 cites W2114675905 @default.
• W2992322182 cites W2114850508 @default.
• W2992322182 cites W2114884926 @default.
• W2992322182 cites W2120518061 @default.
• W2992322182 cites W2130783116 @default.
• W2992322182 cites W2134182833 @default.
• W2992322182 cites W2140065081 @default.
• W2992322182 cites W2157362913 @default.
• W2992322182 cites W2158476854 @default.
• W2992322182 cites W2160714946 @default.
• W2992322182 cites W2162574056 @default.
• W2992322182 cites W2165885799 @default.
• W2992322182 cites W2176711441 @default.
• W2992322182 cites W2205148961 @default.
• W2992322182 cites W2233041362 @default.
• W2992322182 cites W2266439690 @default.
• W2992322182 cites W2307269482 @default.
• W2992322182 cites W2326870000 @default.
• W2992322182 cites W2343073798 @default.
• W2992322182 cites W2414143500 @default.
• W2992322182 cites W2417272797 @default.
• W2992322182 cites W2528445598 @default.
• W2992322182 cites W2549224827 @default.
• W2992322182 cites W2588259746 @default.
• W2992322182 cites W2597129987 @default.
• W2992322182 cites W2607186664 @default.
• W2992322182 cites W2612299843 @default.
• W2992322182 cites W2615034605 @default.
• W2992322182 cites W2686732860 @default.
• W2992322182 cites W2727705276 @default.
• W2992322182 cites W2738925124 @default.
• W2992322182 cites W2742221430 @default.
• W2992322182 cites W2761385332 @default.
• W2992322182 cites W2764000439 @default.
• W2992322182 cites W2766881846 @default.
• W2992322182 cites W2777469091 @default.
• W2992322182 cites W2781887390 @default.
• W2992322182 cites W2797967938 @default.
• W2992322182 cites W2803185089 @default.
• W2992322182 cites W2803368411 @default.
• W2992322182 cites W2913365007 @default.
• W2992322182 cites W2917305085 @default.
• W2992322182 cites W2944930815 @default.
• W2992322182 cites W2950007043 @default.
• W2992322182 cites W2951667064 @default.

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