Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules
| Autor: | Lan, Huan, Abualrous, Esam T., Sticht, Jana, Fernandez, Laura Maria Arroyo, Werk, Tamina, Weise, Christoph, Ballaschk, Martin, Schmieder, Peter, Loll, Bernhard, Freund, Christian |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Protein Conformation
alpha-Helical Antigen Presentation Science Histocompatibility Antigens Class I Immunoglobulins Membrane Proteins Membrane Transport Proteins chemical and pharmacologic phenomena Molecular Dynamics Simulation Crystallography X-Ray Article Recombinant Proteins NMR spectroscopy Allosteric Regulation Enzyme mechanisms Mutation MHC class I Biocatalysis Humans 500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften Nuclear Magnetic Resonance Biomolecular Alleles |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The repertoire of peptides presented by major histocompatibility complex class I (MHC-I) molecules on the cell surface is tailored by the ER-resident peptide loading complex (PLC), which contains the exchange catalyst tapasin. Tapasin stabilizes MHC-I molecules and promotes the formation of stable peptide-MHC-I (pMHC-I) complexes that serve as T cell antigens. Exchange of suboptimal by high-affinity ligands is catalyzed by tapasin, but the underlying mechanism is still elusive. Here we analyze the tapasin-induced changes in MHC-I dynamics, and find the catalyst to exploit two essential features of MHC-I. First, tapasin recognizes a conserved allosteric site underneath the α2-1-helix of MHC-I, ‘loosening’ the MHC-I F-pocket region that accomodates the C-terminus of the peptide. Second, the scoop loop11–20 of tapasin relies on residue L18 to target the MHC-I F-pocket, enabling peptide exchange. Meanwhile, tapasin residue K16 plays an accessory role in catalysis of MHC-I allotypes bearing an acidic F-pocket. Thus, our results provide an explanation for the observed allele-specificity of catalyzed peptide exchange. Tapasin is part of the peptide loading complex necessary for presenting antigenic peptides on MHC-I for the induction of adaptive immunity. Here the authors show that tapasin interacts with MHC-I in both conserved and allele-specific regions to promote antigen presentation, with tapasin L18 and K16 residues both implicated in this molecular interaction. |
| Databáze: | OpenAIRE |
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