Structural insight on the recognition of surface-bound opsonins by the integrin I domain of complement receptor 3
Structural insight on the recognition of surface-bound opsonins by the integrin I domain of complement receptor 3
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DOI：
10.1073/pnas.1311261110
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发表时间：
2013-10-08
影响因子：
11.1
通讯作者：
Andersen, Gregers R.
中科院分区：
文献类型：
--
作者：
Bajic, Goran;Yatime, Laure;Andersen, Gregers R.
补体受体（CRs）在髓细胞和淋巴细胞中表达，在消除补体调理的病原体和凋亡/坏死细胞中发挥重要作用。此外，这些受体对于免疫系统的先天和适应性分支之间的串扰至关重要。CR3(也称为Mac-1、整合素α （M) β(2)或CD11b/CD18）在所有巨噬细胞上表达，并识别补体调理对象上的iC3b，使其吞噬。我们证明了iC3b的C3d部分包含CR3 α I结构域的结合位点，并且我们的C3d: α I结构域复合物的结构使iC3b对CR3的选择性合理化。基于广泛的结构分析，我们认为选择谷氨酸配体或天冬氨酸配体来协调受体金属离子依赖的粘附位点结合金属离子是由配体的二级结构决定的。将我们的结构与CR2:C3d复合物进行比较，并在体外形成稳定的CR3:C3d:CR2复合物，这表明巨噬细胞将CR3结合的免疫复合物转移到淋巴结中CR2呈递细胞的分子机制。
Complement receptors (CRs), expressed notably on myeloid and lymphoid cells, play an essential function in the elimination of complement-opsonized pathogens and apoptotic/necrotic cells. In addition, these receptors are crucial for the cross-talk between the innate and adaptive branches of the immune system. CR3 (also known as Mac-1, integrin alpha(M)beta(2), or CD11b/CD18) is expressed on all macrophages and recognizes iC3b on complement-opsonized objects, enabling their phagocytosis. We demonstrate that the C3d moiety of iC3b harbors the binding site for the CR3 alpha I domain, and our structure of the C3d: alpha I domain complex rationalizes the CR3 selectivity for iC3b. Based on extensive structural analysis, we suggest that the choice between a ligand glutamate or aspartate for coordination of a receptor metal ion-dependent adhesion site-bound metal ion is governed by the secondary structure of the ligand. Comparison of our structure to the CR2:C3d complex and the in vitro formation of a stable CR3:C3d:CR2 complex suggests a molecular mechanism for the hand-over of CR3-bound immune complexes from macrophages to CR2-presenting cells in lymph nodes.