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人中性粒细胞明胶酶相关脂质运载蛋白以及大鼠和小鼠中的同源蛋白。

Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse.

作者信息

Kjeldsen L, Cowland J B, Borregaard N

机构信息

The Granulocyte Research Laboratory, Department of Hematology, The National University Hospital, L-4042, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.

出版信息

Biochim Biophys Acta. 2000 Oct 18;1482(1-2):272-83. doi: 10.1016/s0167-4838(00)00152-7.

DOI:10.1016/s0167-4838(00)00152-7
PMID:11058768
Abstract

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa lipocalin originally purified from human neutrophils. It exists in monomeric and homo- and heterodimeric forms, the latter as a dimer with human neutrophil gelatinase. It is secreted from specific granules of activated human neutrophils. Homologous proteins have been identified in mouse (24p3/uterocalin) and rat (alpha(2)-microglobulin-related protein/neu-related lipocalin). Structural data have confirmed a typical lipocalin fold of NGAL with an eight-stranded beta-barrel, but with an unusually large cavity lined with more polar and positively charged amino acid residues than normally seen in lipocalins. Chemotactic formyl-peptides from bacteria have been proposed as ligands of NGAL, but binding experiments and the structure of NGAL do not support this hypothesis. Besides neutrophils, NGAL is expressed in most tissues normally exposed to microorganisms, and its synthesis is induced in epithelial cells during inflammation. This may indicate either a microbicidal activity of NGAL or a role in regulation of inflammation or cellular growth, putative functions yet to be demonstrated.

摘要

中性粒细胞明胶酶相关脂质运载蛋白(NGAL)是一种最初从人中性粒细胞中纯化出来的25千道尔顿的脂质运载蛋白。它以单体、同二聚体和异二聚体形式存在,后者是与人中性粒细胞明胶酶形成的二聚体。它从活化的人中性粒细胞的特异性颗粒中分泌出来。在小鼠(24p3/子宫珠蛋白)和大鼠(α2-微球蛋白相关蛋白/神经相关脂质运载蛋白)中已鉴定出同源蛋白。结构数据证实NGAL具有典型的脂质运载蛋白折叠结构,即八链β桶状结构,但有一个异常大的腔,腔内排列着比脂质运载蛋白中通常所见更多的极性和带正电荷的氨基酸残基。来自细菌的趋化性甲酰肽被认为是NGAL的配体,但结合实验和NGAL的结构并不支持这一假设。除了中性粒细胞外,NGAL在大多数正常接触微生物组织中表达,并且在炎症过程中上皮细胞中其合成被诱导。这可能表明NGAL具有杀菌活性,或者在炎症调节或细胞生长中发挥作用,但其假定功能尚未得到证实。

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