Crystal structure of human peptidoglycan recognition protein Iα bound to a muramyl pentapeptide from Gram-positive bacteria
Crystal structure of human peptidoglycan recognition protein Iα bound to a muramyl pentapeptide from Gram-positive bacteria
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DOI：
10.1110/ps.062077606
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发表时间：
2006-05-01
期刊：
影响因子：
8
通讯作者：
Mariuzza, RA
中科院分区：
文献类型：
--
作者：
Guan, RJ;Brown, PH;Mariuzza, RA
肽聚糖识别蛋白（PGRP）是先天免疫系统的模式识别受体，其结合细菌肽聚糖（PGN）。我们测定了人PGRP-1 α与来自革兰氏阳性菌的胞壁酰五肽（MPP）复合物的C-末端PGN结合结构域的晶体结构，其含有完整的肽茎（L-Ala-D-isoGln-L-Lys-D-Ala-D-Ala），分辨率为2.1埃。该结构揭示了以前在PGRP-1 α和在茎位置4和5缺乏D-Ala的胞壁酰三肽之间的复合物中未观察到的重要特征。最值得注意的是配体诱导的PGN结合位点的结构重排，这对于进入肽茎的C-末端部分和将MPP锁定在结合沟中是必不可少的。我们建议，类似的结构重排，以适应PGN干可能表征许多PGRP，哺乳动物和昆虫。
Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors of the innate immune system that bind bacterial peptidoglycans (PGNs). We determined the crystal structure, to 2.1 angstrom resolution, of the C-terminal PGN-binding domain of human PGRP-1 alpha in complex with a muramyl pentapeptide (MPP) from Gram-positive bacteria containing a complete peptide stem (L-Ala-D-isoGln-L-Lys-D-Ala-D-Ala). The structure reveals important features not observed previously in the complex between PGRP-1 alpha and a muramyl tripeptide lacking D-Ala at stem positions 4 and 5. Most notable are ligand-induced structural rearrangements in the PGN-binding site that are essential for entry of the C-terminal portion of the peptide stem and for locking MPP in the binding groove. We propose that similar structural rearrangements to accommodate the PGN stem likely characterize many PGRPs, both mammalian and insect.