Solution structure of CXCL5--a novel chemokine and adipokine implicated in inflammation and obesity.
Solution structure of CXCL5--a novel chemokine and adipokine implicated in inflammation and obesity.
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DOI：
10.1371/journal.pone.0093228
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rajarathnam K
中科院分区：
文献类型：
--
作者：
Sepuru KM;Poluri KM;Rajarathnam K
趋化因子CXCL5在高度特化的细胞中选择性表达，如肺上皮II型细胞和肌肉白色脂肪组织巨噬细胞，它介导多种功能，从通过调节中性粒细胞运输对抗微生物感染到通过抑制胰岛素信号传导促进肥胖。目前，关于CXCL5如何介导其新功能的结构基础知之甚少。针对这一缺失的知识，我们通过核磁共振光谱解决了CXCL5二聚体的溶液结构。CXCL5是7个cxcr2激活趋化因子（CAC）子集中的一员，其特征是在n端尾部高度保守的ELR基序。从结构上看，CXCL5采用了典型的趋化因子折叠，但在30 s环和n端残基上也显示出一些明显的差异；毫不奇怪，n端和30s环残基之间的串扰被认为是受体活性的主要决定因素。CAC的功能还涉及与高硫酸化糖胺聚糖（GAG）的结合，CXCL5结构显示出带正电残基的明显分布，表明GAG相互作用的差异也影响功能。该结构的可用性现在应该有助于设计实验，以更好地了解各种CXCL5功能的分子基础，并作为设计用于临床环境的抑制剂的模板。
The chemokine CXCL5 is selectively expressed in highly specialized cells such as epithelial type II cells in the lung and white adipose tissue macrophages in muscle, where it mediates diverse functions from combating microbial infections by regulating neutrophil trafficking to promoting obesity by inhibiting insulin signaling. Currently very little is known regarding the structural basis of how CXCL5 mediates its novel functions. Towards this missing knowledge, we have solved the solution structure of the CXCL5 dimer by NMR spectroscopy. CXCL5 is a member of a subset of seven CXCR2-activating chemokines (CAC) that are characterized by the highly conserved ELR motif in the N-terminal tail. The structure shows that CXCL5 adopts the typical chemokine fold, but also reveals several distinct differences in the 30 s loop and N-terminal residues; not surprisingly, crosstalk between N-terminal and 30 s loop residues have been implicated as a major determinant of receptor activity. CAC function also involves binding to highly sulfated glycosaminoglycans (GAG), and the CXCL5 structure reveals a distinct distribution of positively charged residues, suggesting that differences in GAG interactions also influence function. The availability of the structure should now facilitate the design of experiments to better understand the molecular basis of various CXCL5 functions, and also serve as a template for the design of inhibitors for use in a clinical setting.
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影响因子：
17.1
作者：
Dawes JM;Calvo M;Perkins JR;Paterson KJ;Kiesewetter H;Hobbs C;Kaan TK;Orengo C;Bennett DL;McMahon SB
通讯作者：
McMahon SB
影响因子：
6.7
作者：
Colditz, Ian G.;Schneider, Martin A.;Rot, Antal
通讯作者：
Rot, Antal
影响因子：
3.7
作者：
Das ST;Rajagopalan L;Guerrero-Plata A;Sai J;Richmond A;Garofalo RP;Rajarathnam K
通讯作者：
Rajarathnam K
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
2.9
作者：
FARROW, NA;MUHANDIRAM, R;KAY, LE
通讯作者：
KAY, LE