Crystal structures of the ligand-binding region of uPARAP: effect of calcium ion binding
Crystal structures of the ligand-binding region of uPARAP: effect of calcium ion binding
复制标题
uPARAP 配体结合区的晶体结构：钙离子结合的影响
DOI：
10.1042/bcj20160276
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发表时间：
2016
影响因子：
4.1
通讯作者：
Huang Mingdong
中科院分区：
文献类型：
--
作者：
Yuan Cai;Jurgensen Henrik J;Engelholm Lars H;Li Rui;Liu Min;Jiang Longguang;Luo Zhipu;Behrendt Niels;Huang Mingdong
The proteins of the mannose receptor (MR) family share a common domain organization and have a broad range of biological functions. Urokinase plasminogen activator receptor-associated protein (uPARAP) (or Endo180) is a member of this family and plays an important role in extracellular matrix remodelling through interaction with its ligands, including collagens and urokinase plasminogen activator receptor (uPAR). We report the crystal structures of the first four domains of uPARAP (also named the ligand-binding region, LBR) at pH 7.4 in Ca2+-bound and Ca2+-free forms. The first domain (cysteine-rich or CysR domain) folds into a new and unique conformation different from the β-trefoil fold of typical CysR domains. The so-called long loop regions (LLRs) of the C-type lectin-like domain (CTLD) 1 and 2 (the third and fourth domain) mediate the direct contacts between these domains. These LLRs undergo a Ca2+-dependent conformational change, and this is likely to be the key structural determinant affecting the overall conformation of uPARAP. Our results provide a molecular mechanism to support the structural flexibility of uPARAP, and shed light on the structural flexibility of other members of the MR family.
