Endogenous peptides of a soluble major histocompatibility complex class I molecule, H-2Lds: sequence motif, quantitative binding, and molecular modeling of the complex.
Endogenous peptides of a soluble major histocompatibility complex class I molecule, H-2Lds: sequence motif, quantitative binding, and molecular modeling of the complex.
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DOI：
10.1084/jem.176.6.1681
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发表时间：
1992-12-01
期刊：
影响因子：
--
通讯作者：
Margulies DH
中科院分区：
文献类型：
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作者：
Corr M;Boyd LF;Frankel SR;Kozlowski S;Padlan EA;Margulies DH
为了深入了解的规则，管理的内源性和病毒肽的结合到一个给定的主要组织相容性复合体（MHC）I类分子，我们的特点是一组自身肽结合的可溶性类似物的小鼠H-2Ld，H-2Lds的氨基酸序列。我们在几种不同的测定中定量测试了相应的合成肽的结合，并基于人HLA-B27/肽复合物的晶体结构建立了八种肽/H-2 Lds复合物的三维计算机模型。结合自身和抗原肽的一级和三级结构的比较表明，残基2和9不仅在序列上受到限制，并容忍保守取代，但在三维模型中的空间限制。MHC限制性肽中特定残基的序列变异程度反映了这些氨基酸缺乏结构约束。因此，限定肽基序的氨基酸残基代表与MHC I类重链紧密配合所需或优选的侧链。
To gain insight into the rules that govern the binding of endogenous and viral peptides to a given major histocompatibility complex (MHC) class I molecule, we characterized the amino acid sequences of a set of self peptides bound by a soluble analogue of murine H-2Ld, H-2Lds. We tested corresponding synthetic peptides quantitatively for binding in several different assays, and built three-dimensional computer models of eight peptide/H-2Lds complexes, based on the crystallographic structure of the human HLA-B27/peptide complex. Comparison of primary and tertiary structures of bound self and antigenic peptides revealed that residues 2 and 9 were not only restricted in sequence and tolerant of conservative substitutions, but were spatially constrained in the three-dimensional models. The degree of sequence variability of specific residues in MHC-restricted peptides reflected the lack of structural constraint on those amino acids. Thus, amino acid residues that define a peptide motif represent side chains required or preferred for a close fit with the MHC class I heavy chain.