5EW6

Structure of ligand binding region of uPARAP at pH 7.4 without calcium

Summary for 5EW6

• Entry DOI: 10.2210/pdb5ew6/pdb
• Related: 5E4K
• Related PRD ID: PRD_900017
• Descriptor: C-type mannose receptor 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, SODIUM ION, ... (6 entities in total)
• Functional Keywords: endocytic collagen receptor, sugar binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Membrane; Single-pass type I membrane protein: Q9UBG0
• Total number of polymer chains: 1
• Total formula weight: 57014.90

Authors

Yuan, C.,Huang, M. (deposition date: 2015-11-20, release date: 2016-08-10, Last modification date: 2023-11-08)

Primary citation

Yuan, C.,Jurgensen, H.J.,Engelholm, L.H.,Li, R.,Liu, M.,Jiang, L.,Luo, Z.,Behrendt, N.,Huang, M.
Crystal structures of the ligand-binding region of uPARAP: effect of calcium ion binding
Biochem.J., 473:2359-2368, 2016

PubMed Abstract: 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 Ca(2+)-bound and Ca(2+)-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 Ca(2+)-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.

PubMed: 27247422
DOI: 10.1042/BCJ20160276

Experimental method

X-RAY DIFFRACTION (2.29 Å)