Disruption of hydrogen bonds between major histocompatibility complex class II and the peptide N-terminus is not sufficient to form a human leukocyte antigen-DM receptive state of major histocompatibility complex class II.
Disruption of hydrogen bonds between major histocompatibility complex class II and the peptide N-terminus is not sufficient to form a human leukocyte antigen-DM receptive state of major histocompatibility complex class II.
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DOI：
10.1371/journal.pone.0069228
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Call MJ
中科院分区：
文献类型：
--
作者：
Schulze MS;Anders AK;Sethi DK;Call MJ
MHC-II类分子的多肽递呈对CD4+T细胞的功能至关重要。HL A-DM位于内体途径中，在新合成的MHC II类分子输出到细胞表面之前对其进行编辑。HL A-DM通过靶向不稳定的MHC II类：多肽复合体进行肽交换，确保MHC II类分子与高亲和力的多肽结合。过去十年的研究表明，多肽N-末端参与调节人类白细胞抗原-糖尿病靶向特定MHC II类的能力：多肽组合。特别是，人们的注意力集中在MHC II类分子和多肽之间的氢键以及P1锚囊的占有率上。我们试图解决一个含有截短的血凝素多肽的HLA-DR1分子的晶体结构，与全长序列(残基306-318)相比，缺少三个N-末端残基，以确定MHC II类：结合HLA-DM的多肽物种的性质。在这里，我们提供了结构证据，即负载了被截断到P1锚基残基的多肽而不能与多肽N-末端形成选择性氢键的HLA-DR1，采用了与负载全长多肽的分子相同的构象。HL A-DR1：不能结合四个关键氢键的多肽组合也不能结合HLA-DM，而那些截短到P2残基的多肽组合结合得很好。这些结果表明，被HLA-DM识别的MHC II类分子的构象变化发生在P1锚基残基解离之后。
Peptide presentation by MHC class II is of critical importance to the function of CD4+ T cells. HLA-DM resides in the endosomal pathway and edits the peptide repertoire of newly synthesized MHC class II molecules before they are exported to the cell surface. HLA-DM ensures MHC class II molecules bind high affinity peptides by targeting unstable MHC class II:peptide complexes for peptide exchange. Research over the past decade has implicated the peptide N-terminus in modulating the ability of HLA-DM to target a given MHC class II:peptide combination. In particular, attention has been focused on both the hydrogen bonds between MHC class II and peptide, and the occupancy of the P1 anchor pocket. We sought to solve the crystal structure of a HLA-DR1 molecule containing a truncated hemagglutinin peptide missing three N-terminal residues compared to the full-length sequence (residues 306–318) to determine the nature of the MHC class II:peptide species that binds HLA-DM. Here we present structural evidence that HLA-DR1 that is loaded with a peptide truncated to the P1 anchor residue such that it cannot make select hydrogen bonds with the peptide N-terminus, adopts the same conformation as molecules loaded with full-length peptide. HLA-DR1:peptide combinations that were unable to engage up to four key hydrogen bonds were also unable to bind HLA-DM, while those truncated to the P2 residue bound well. These results indicate that the conformational changes in MHC class II molecules that are recognized by HLA-DM occur after disengagement of the P1 anchor residue.
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影响因子：
32.4
作者：
Doebele, RC;Busch, R;Mellins, ED
通讯作者：
Mellins, ED
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
64.8
作者：
LANZAVECCHIA, A;REID, PA;WATTS, C
通讯作者：
WATTS, C
影响因子：
4.4
作者：
Nicholson, Melissa J.;Moradi, Babak;Wucherpfennig, Kai W.
通讯作者：
Wucherpfennig, Kai W.
影响因子：
4.4
作者：
Ferrante, Andrea;Gorski, Jack
通讯作者：
Gorski, Jack