9fse

Human ROR2 cysteine-rich domain (CRD) and Kringle domain

spinqualitylabelsall models 9fse, resolution 2.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9fse is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.48Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease ROR2_HUMAN Autosomal recessive Robinow syndrome;Brachydactyly type B. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function ROR2_HUMAN Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes. It seems to be required for cartilage and growth plate development. Phosphorylates YWHAB, leading to induction of osteogenesis and bone formation. Publication Abstract from PubMed The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, brachydactyly B, and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals. Structure and function of the ROR2 cysteine-rich domain in vertebrate noncanonical WNT5A signaling.,Griffiths SC, Tan J, Wagner A, Blazer LL, Adams JJ, Srinivasan S, Moghisaei S, Sidhu SS, Siebold C, Ho HH Elife. 2024 May 23;13:e71980. doi: 10.7554/eLife.71980. PMID:38780011 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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