5ao5
From Proteopedia
Endo180 D1-4, monoclinic form
Structural highlights
FunctionMRC2_HUMAN May play a role as endocytotic lectin receptor displaying calcium-dependent lectin activity. Internalizes glycosylated ligands from the extracellular space for release in an endosomal compartment via clathrin-mediated endocytosis. May be involved in plasminogen activation system controlling the extracellular level of PLAUR/PLAU, and thus may regulate protease activity at the cell surface. May contribute to cellular uptake, remodeling and degradation of extracellular collagen matrices. May play a role during cancer progression as well as in other chronic tissue destructive diseases acting on collagen turnover. May participate in remodeling of extracellular matrix cooperating with the matrix metalloproteinases (MMPs).[1] [2] Publication Abstract from PubMedThe C-type mannose receptor and its homolog Endo180 (or uPARAP, for urokinase plasminogen activator receptor-associated protein) mediate the endocytic uptake of collagen by macrophages and fibroblasts. This process is required for normal tissue remodeling, but also facilitates the growth and dissemination of tumors. We have determined the crystal structure at 2.5 A resolution of the N-terminal region of Endo180, consisting of a ricin-like domain, a fibronectin type II (FN2) domain, and two C-type lectin (CTL) domains. The L-shaped arrangement of these domains creates a shallow trench spanning the FN2 and CTL1 domains, which was shown by mutagenesis to bind triple-helical and denatured collagen. Small-angle X-ray scattering showed that the L-shaped structure is maintained in solution at neutral and acidic pH, irrespective of calcium ion loading. Collagen binding was equally unaffected by acidic pH, suggesting that collagen release in endosomes is not regulated by changes within the Endo180 N-terminal region. Insights into Collagen Uptake by C-type Mannose Receptors from the Crystal Structure of Endo180 Domains 1-4.,Paracuellos P, Briggs DC, Carafoli F, Loncar T, Hohenester E Structure. 2015 Nov 3;23(11):2133-42. doi: 10.1016/j.str.2015.09.004. Epub 2015, Oct 15. PMID:26481812[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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