Structure of the fungal β-glucan-binding immune receptor dectin-1:: Implications for function

被引:128
作者
Brown, James
O'Callaghan, Chris A.
Marshall, Andrew S. J.
Gilbert, Robert J. C.
Siebold, Christian
Gordon, Siamon
Brown, Gordon D.
Jones, E. Yvonne
机构
[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, CR UK Receptor Struct Res Grp, Oxford OX3 7BN, England
[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[3] Univ Cape Town, Fac Hlth Sci, CLS, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa
基金
英国医学研究理事会; 英国惠康基金;
关键词
immune recognition; fungal pathogen; beta-glucan; protein crystallography; C-type lectin-like domain;
D O I
10.1110/ps.072791207
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The murine molecule dectin-1 (known as the beta-glucan receptor in humans) is an immune cell surface receptor implicated in the immunological defense against fungal pathogens. Sequence analysis has indicated that the dectin-1 extracellular domain is a C-type lectin-like domain, and functional studies have established that it binds fungal beta-glucans. We report several dectin-1 crystal structures, including a high-resolution structure and a 2.8 angstrom resolution structure in which a short soaked natural beta-glucan is trapped in the crystal lattice. In vitro characterization of dectin-1 in the presence of its natural ligand indicates higher-order complex formation between dectin-1 and beta-glucans. These combined structural and biophysical data considerably extend the current knowledge of dectin-1 structure and function, and suggest potential mechanisms of defense against fungal pathogens.
引用
收藏
页码:1042 / 1052
页数:11
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