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通过异核核磁共振研究的CINC/Gro的溶液结构。

Solution structure of CINC/Gro investigated by heteronuclear NMR.

作者信息

Hanzawa H, Haruyama H, Konishi K, Watanabe K, Tsurufuji S

机构信息

Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd., Tokyo.

出版信息

J Biochem. 1998 Jan;123(1):62-70. doi: 10.1093/oxfordjournals.jbchem.a021917.

DOI:10.1093/oxfordjournals.jbchem.a021917
PMID:9504410
Abstract

Cytokine-induced neutrophil chemoattractant (CINC/Gro) is a chemotactic factor for neutrophils in the rat and a member of the CXC chemokine family. The refined three-dimensional structure of CINC/Gro was derived with the aid of heteronuclear magnetic resonance spectroscopy and a hybrid method of distance geometry and simulated annealing. The backbone atomic r.m.s. differences for 19 structures about the mean coordinates for residues 7 to 70 are 0.69+/-0.15 A for the dimer and 0.56+/-0.13 A for the monomer. The N terminal region containing an ELR sequence, an essential motif for chemotactic activity, is disordered in solution, as in other CXC chemokines. The dimer structure consists of a six-stranded anti-parallel beta sheet with two C-terminal alpha helices on the beta sheet. The overall dimer structure of CINC/Gro is similar to that of human MGSA, though the backbone r.m.s.d.s between CINC/Gro and the two MGSA structures were high (1.81 and 2.34 A for the monomer) in spite of the high sequence homology (67%). The major difference resides in the relative position of the C-terminal alpha helix with respect to the beta sheet. This results in a difference of interhelical distances in the dimer: wider (15 A) in CINC/Gro, as in IL-8, than in MGSA (11.7 and 10 A).

摘要

细胞因子诱导的中性粒细胞趋化因子(CINC/Gro)是大鼠中性粒细胞的一种趋化因子,属于CXC趋化因子家族成员。借助异核磁共振波谱以及距离几何和模拟退火的混合方法,得出了CINC/Gro精细的三维结构。关于残基7至70的平均坐标,19个结构的主链原子均方根偏差,二聚体为0.69±0.15 Å,单体为0.56±0.13 Å。与其他CXC趋化因子一样,含有ELR序列(趋化活性的必需基序)的N端区域在溶液中无序。二聚体结构由一个六链反平行β折叠组成,β折叠上有两个C端α螺旋。CINC/Gro的整体二聚体结构与人类MGSA的相似,尽管CINC/Gro与两种MGSA结构之间的主链均方根偏差很高(单体分别为1.81和2.34 Å),尽管序列同源性很高(67%)。主要差异在于C端α螺旋相对于β折叠的相对位置。这导致二聚体中螺旋间距离存在差异:CINC/Gro中更宽(15 Å),与IL-8一样,比MGSA(11.7和10 Å)宽。

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