Structural basis for peptidoglycan binding by peptidoglycan recognition proteins
Structural basis for peptidoglycan binding by peptidoglycan recognition proteins
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DOI：
10.1073/pnas.0407856101
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发表时间：
2004-12-07
影响因子：
11.1
通讯作者：
Mariuzza, RA
中科院分区：
文献类型：
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作者：
Guan, RJ;Roychowdhury, A;Mariuzza, RA
肽聚糖(PGN)识别蛋白(PGRPs)是天然免疫系统的模式识别受体，结合细菌PGN，在某些情况下还能降解细菌PGN。在2.30埃分辨率下，我们测定了人PGRP-Ipha与代表革兰氏阳性菌赖氨酸型PGN核心的胞壁三肽的复合体的晶体结构。配体的肽茎埋在一个长结合槽的深端，N-乙酰胞壁酸位于槽的中间，其浅端可以容纳连接的N-乙酰氨基葡萄糖。尽管大多数相互作用是与多肽相互作用的，但多糖部分似乎对PGRPs的特异性识别也是必不可少的。对关键的PGN接触残基的保守表明，所有的PGRPs都采用这种基本的PGN结合模式。该结构精确定位可变残基，这些残基可能介导赖氨酸和二氨基戊二酸类型的PGN之间的区别。我们还提出了一种含锌的PGRPs对PGN的水解机理。
Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern-recognition receptors of the innate immune system that bind and, in some cases, hydrolyze bacterial PGNs. We determined the crystal structure, at 2.30-Angstrom resolution, of the C-terminal PGN-binding domain of human PGRP-Ialpha in complex with a muramyl tripeptide representing the core of lysine-type PGNs from Gram-positive bacteria. The peptide stem of the ligand is buried at the deep end of a long binding groove, with N-acetylmuramic acid situated in the middle of the groove, whose shallow end can accommodate a linked N-acetylglucosamine. Although most interactions are with the peptide, the glycan moiety also seems to be essential for specific recognition by PGRPs. Conservation of key PGN-contacting residues shows that all PGRPs employ this basic PGN-binding mode. The structure pinpoints variable residues that likely mediate discrimination between lysine- and diaminopimelic acid-type PGNs. We also propose a mechanism for PGN hydrolysis by Zn2+-containing PGRPs.