β2整合素CR3（CD11b/CD18）A结构域中的一个新型二价阳离子结合位点对于配体结合至关重要。

A novel divalent cation-binding site in the A domain of the beta 2 integrin CR3 (CD11b/CD18) is essential for ligand binding.

作者信息

Michishita M, Videm V, Arnaout M A

机构信息

Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown 02129.

出版信息

Cell. 1993 Mar 26;72(6):857-67. doi: 10.1016/0092-8674(93)90575-b.

DOI:10.1016/0092-8674(93)90575-b

PMID:8458080

Abstract

A recombinant peptide encoding the CD11b A domain bound 54Mn2+ with a high affinity. Other divalent cations, including Mg2+, Zn2+, Ni2+, Co2+, and Cd2+, but not Ca2+ or Ba2+, competed effectively for Mn2+ binding. Amino acid substitutions within two conserved and noncontiguous regions in the recombinant peptide abolished 54Mn2+ binding. When these substitutions were introduced independently in complement receptor type 3 (CR3), each abolished the metal-dependent binding of the receptor to the major C3 opsonin iC3b, without impairing subunit association or surface expression of the receptor. These findings identify an unsuspected and novel metal-binding site within the A domain of CR3 that is required for metal-dependent ligand binding and also identify a good target for designing drugs aimed at countering the inflammatory potential of this key receptor.

摘要

一种编码CD11b A结构域的重组肽能以高亲和力结合54Mn2+。包括Mg2+、Zn2+、Ni2+、Co2+和Cd2+在内的其他二价阳离子能有效竞争Mn2+的结合，但Ca2+或Ba2+不能。重组肽中两个保守且不相邻区域内的氨基酸替换消除了54Mn2+的结合。当这些替换分别引入3型补体受体（CR3）时，每种替换都消除了该受体与主要C3调理素iC3b的金属依赖性结合，而不影响亚基缔合或受体的表面表达。这些发现确定了CR3的A结构域内一个未曾预料到的新型金属结合位点，该位点是金属依赖性配体结合所必需的，同时也确定了一个针对该关键受体的抗炎潜力设计药物的良好靶点。