Three-dimensional structure of H-2Dd complexed with an immunodominant peptide from human immunodeficiency virus envelope glycoprotein 120
Three-dimensional structure of H-2Dd complexed with an immunodominant peptide from human immunodeficiency virus envelope glycoprotein 120
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DOI：
10.1006/jmbi.1998.2091
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发表时间：
1998-10-16
影响因子：
5.6
通讯作者：
Mariuzza, RA
中科院分区：
文献类型：
--
作者：
Li, HM;Natarajan, K;Mariuzza, RA
在3.2埃分辨率下测定了小鼠主要组织相容性复合体(MHC)I类分子H-2D(D)与人类免疫缺陷病毒包膜糖蛋白120的免疫优势肽P18-I10(RGPGRAFVTI)的晶体结构。DD的α3结构域相对于α1/α2结构域的新方向导致与其他MHC I类蛋白相比，α3与β(2)-微球蛋白之间的接触显著减少。十分之四的多肽残基(P2Gly、P3Pro、P5Arg和P10Ile)几乎完全埋在D-d结合槽中。这与以前的研究结果一致，即D-d利用了一个四个残基的结合基序，该基序包括P2的甘氨酸，P3的脯氨酸，P5的正电荷残基，以及P9或P10的C末端疏水残基。P5 Arg的侧链指向以疏水为主的结合槽的底部，在那里它与D-d残基Asp77形成两个盐桥和一个氢键。P2处甘氨酸的选择似乎是由于Arg66引起的B口袋相对于其他I类分子的狭窄，其侧链向下折叠进入结合裂隙。P18-I10的残基P3Pro占据了口袋D的一部分，在D-d中，口袋D被Trp97和Trp114形成的结合槽底部的显著疏水脊部分劈开。残基P6到P9形成一个暴露在溶剂中的凸起，其中P7Phe从结合槽突出最多，因此可能构成与T细胞受体相互作用的主要部位。将H-2D(D)/P18-I10与其他已知结构的MHC-I类/肽复合物进行比较，可以深入了解自然杀伤细胞受体Ly-49A与几个相关的I类分子的特异性的可能基础。(C)1998年学术出版社。
The crystal structure of the mouse major histocompatibility complex (MHC) class I molecule H-2D(d) with an immunodominant peptide, designated P18-I10 (RGPGRAFVTI), from human immunodeficiency virus envelope glycoprotein 120 was determined at 3.2 Angstrom resolution. A novel orientation of the alpha 3 domain of Dd relative to the alpha 1/alpha 2 domains results in significantly fewer contacts between alpha 3 and beta(2)-microglobulin compared with other MHC class I proteins. Four out of ten peptide residues (P2 Gly, P3 Pro, P5 Arg and P10 Ile) are nearly completely buried in the D-d binding groove. This is consistent with previous findings that D-d exploits a four-residue binding motif comprising a glycine at P2, a proline at P3, a positively charged residue at P5, and a C-terminal hydrophobic residue at P9 or P10. The side-chain of P5 Arg is directed toward the floor of the predominantly hydrophobic binding groove where it forms two salt bridges and one hydrogen bond with D-d residue Asp77. The selection of glycine at P2 appears to be due to a narrowing of the B pocket, relative to that of other class I molecules, caused by Arg66 whose side-chain folds down into the binding cleft. Residue P3 Pro of P18-I10 occupies part of pocket D, which in D-d is partially split by a prominent hydrophobic ridge in the floor of the binding groove formed by Trp97 and Trp114. Residues P6 through P9 form a solvent-exposed bulge, with P7 Phe protruding the most from the binding groove and thereby probably constituting a major site of interaction with T cell receptors. A comparison of H-2D(d)/P18-I10 with other MHC class I/peptide complexes of known structure provides insights into the possible basis for the specificity of the natural killer cell receptor Ly-49A for several related class I molecules. (C) 1998 Academic Press.