Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules.
Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules.
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DOI：
10.1038/s41467-021-24401-4
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发表时间：
2021-07-09
影响因子：
16.6
通讯作者：
Freund C
中科院分区：
文献类型：
--
作者：
Lan H;Abualrous ET;Sticht J;Fernandez LMA;Werk T;Weise C;Ballaschk M;Schmieder P;Loll B;Freund C
细胞表面主要组织相容性复合体I类(MHC-I)分子呈递的多肽是由内质网驻留的多肽负载复合体(PLC)定制的，其中包含交换催化剂Tapasin。Tapasin稳定MHC-I分子，促进稳定的多肽-MHC-I(pMHC-I)复合体的形成，作为T细胞抗原。高亲和力配体的次优交换是由Tapasin催化的，但其潜在的机制仍不清楚。在这里，我们分析了Tapasin诱导的MHC-I动力学变化，并找到了开发MHC-I的两个基本特征的催化剂。首先，Tapasin识别MHC-I的α2-1-螺旋下的保守变构部位，‘松开’容纳多肽C-末端的MHC-I F-袋区。其次，Tapasin的勺环11-20依靠残基L18靶向MHC-I F-Pocket，实现肽交换。同时，Tapasin残基K16在含有酸性F-口袋的MHC-I同种异型的催化中起辅助作用。因此，我们的结果为观察到的催化多肽交换的等位基因特异性提供了解释。Tapasin是多肽负载复合体的一部分，是在MHC-I上呈递抗原肽以诱导适应性免疫所必需的。在这里，作者表明，Tapasin与MHC-I在保守区和等位基因特异性区域相互作用，以促进抗原提呈，Tapasin L18和K16残基都参与了这种分子相互作用。
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.
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影响因子：
32.4
作者：
Dong, Gang;Wearsch, Pamela A.;Peaper, David R.;Cresswell, Peter;Reinisch, Karin M.
通讯作者：
Reinisch, Karin M.
影响因子：
3.7
作者：
Abualrous ET;Saini SK;Ramnarayan VR;Ilca FT;Zacharias M;Springer S
通讯作者：
Springer S
DOI：
10.1073/pnas.2013554117
发表时间：
2020-11-10
影响因子：
11.1
作者：
Bashirova AA;Viard M;Naranbhai V;Grifoni A;Garcia-Beltran W;Akdag M;Yuki Y;Gao X;O'hUigin C;Raghavan M;Wolinsky S;Bream JH;Duggal P;Martinson J;Michael NL;Kirk GD;Buchbinder SP;Haas D;Goedert JJ;Deeks SG;Fellay J;Walker B;Goulder P;Cresswell P;Elliott T;Sette A;Carlson J;Carrington M
通讯作者：
Carrington M
影响因子：
11.4
作者：
Chen, Mingnan;Bouvier, Marlene
通讯作者：
Bouvier, Marlene
DOI：
10.1073/pnas.1222342110
发表时间：
2013-02-26
影响因子：
11.1
作者：
Boyle, Louise H.;Hermann, Clemens;Trowsdale, John
通讯作者：
Trowsdale, John