Peptidoglycan recognition by Pal, an outer membrane lipoprotein
Peptidoglycan recognition by Pal, an outer membrane lipoprotein
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DOI：
10.1021/bi052227i
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发表时间：
2006-02-21
期刊：
影响因子：
2.9
通讯作者：
Orban, J
中科院分区：
文献类型：
--
作者：
Parsons, LM;Lin, F;Orban, J
肽聚糖相关脂蛋白（Peptidoglycan-associated lipoprotein，PGL）是一种潜在的流感嗜血杆菌疫苗候选物，在革兰氏阴性菌中高度保守，通过N-末端脂质附着锚定在外膜上。通过周质结构域提供与肽聚糖（PG）层的非共价连接，从而稳定外膜。使用NMR光谱，我们确定了胞壁周质结构域和生物合成肽聚糖前体（PG-P）UDP-N-乙酰胞壁酰-L-Ala-α-D-Glu-m-Dap-D-Ala-D-Ala（m-Dap是meso-diaminopimelate）之间复合物的三维结构。配体具有排列有保守的表面残基的结合口袋，其仅与配体的肽部分相互作用。主要存在于革兰氏阴性菌细胞壁中的m-Dap残基被隔离在该口袋中，并通过与细菌形成氢键和疏水接触而发挥重要作用。该结构提供了深入了解细胞壁的模式识别的一个广泛的类别的革兰氏阴性膜蛋白，包括OmpA和MotB，其具有肽聚糖结合域同源的peptidoglycan。
Peptidoglycan-associated lipoprotein (Pal) is a potential vaccine candidate from Haemophilus influenzae that is highly conserved in Gram-negative bacteria and anchored to the outer membrane through an N-terminal lipid attachment. Pal stabilizes the outer membrane by providing a noncovalent link to the peptidoglycan (PG) layer through a periplasmic domain. Using NMR spectroscopy, we determined the three-dimensional structure of a complex between the periplasmic domain of Pal and a biosynthetic peptidoglycan precursor (PG-P), UDP-N-acetylmuramyl-L-Ala-alpha-D-Glu-m-Dap-D-Ala-D-Ala (m-Dap is meso-diaminopimelate). Pal has a binding pocket lined with conserved surface residues that interacts exclusively with the peptide portion of the ligand. The m-Dap residue, which is mainly found in the cell walls of Gram-negative bacteria, is sequestered in this pocket and plays an important role by forming hydrogen bond and hydrophobic contacts to Pal. The structure provides insight into the mode of cell wall recognition for a broad class of Gram-negative membrane proteins, including OmpA and MotB, which have peptidoglycan-binding domains homologous to that of Pal.