Crystal structure of human peptidoglycan recognition protein S (PGRP-S) at 1.70 Å resolution
Crystal structure of human peptidoglycan recognition protein S (PGRP-S) at 1.70 Å resolution
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DOI：
10.1016/j.jmb.2005.01.070
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发表时间：
2005-04-08
影响因子：
5.6
通讯作者：
Mariuzza, RA
中科院分区：
文献类型：
--
作者：
Guan, RJ;Wang, Q;Mariuzza, RA
肽聚糖识别蛋白 (PGRP) 是先天免疫系统的模式识别受体，可结合细菌细胞壁的肽聚糖 (PGN)。这些分子从昆虫到哺乳动物都高度保守，有助于宿主防御革兰氏阳性和革兰氏阴性细菌的感染。在这里，我们以 1.70 埃的分辨率展示了人类 PGRP-S 的晶体结构。参与细胞内杀灭革兰氏阳性菌的PGRP-S的整体结构与其他PGRP相似，包括果蝇PGRP-LB和PGRP-SA以及人PGRP-Iα。然而，与这些 PGRP 的比较揭示了 PGN 结合位点和分子反面 PGRP 特异性片段形成的凹槽的重要差异。该凹槽可能构成效应蛋白或信号蛋白的结合位点，与 PGRP-I α C 相比，PGRP-S 中的疏水性更小且更深，而 PGRP-I α C 的 PGRP 特异性片段的氨基酸序列差异很大。基于PGRP-I α-PGN复合物的已知结构，通过将PGN配体对接至PGRP-S的PGN结合裂口，我们鉴定了PGRP-S中潜在的PGN结合残基。 PGN 接触残基和相互作用的差异表明，尽管 PGRP 可能以类似的模式与 PGN 结合，但存在结构差异，可能调节 PGN 识别的亲和力和精细特异性。 (c) 2005 Elsevier Ltd. 保留所有权利。
Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of the innate immune system that bind peptidoglycans (PGNs) of bacterial cell walls. These molecules, which are highly conserved from insects to mammals, contribute to host defense against infections by both Gram-positive and Gram-negative bacteria. Here, we present the crystal structure of human PGRP-S at 1.70 angstrom resolution. The overall structure of PGRP-S, which participates in intracellular killing of Gram-positive bacteria, is similar to that of other PGRPs, including Drosophila PGRP-LB and PGRP-SA and human PGRP-I alpha. However, comparison with these PGRPs reveals important differences in both the PGN-binding site and a groove formed by the PGRP-specific segment on the opposite face of the molecule. This groove, which may constitute a binding site for effector or signaling proteins, is less hydrophobic and deeper in PGRP-S than in PGRP-I alpha C, whose PGRP-specific segments vary considerably in amino acid sequence. By docking a PGN ligand into the PGN-binding cleft of PGRP-S based on the known structure of a PGRP-I alpha-PGN complex, we identified potential PGN-binding residues in PGRP-S. Differences in PGN-contacting residues and interactions suggest that, although PGRPs may engage PGNs in a similar mode, structural differences exist that likely regulate the affinity and fine specificity of PGN recognition. (c) 2005 Elsevier Ltd. All rights reserved.