5yh2

The structure of DrFam20C1 and hFam20A complex

spinqualitylabelsall models 5yh2, resolution 3.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5yh2 is a 4 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.55Å Ligands: ATP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease FA20A_HUMAN Amelogenesis imperfecta - nephrocalcinosis;Amelogenesis imperfecta and gingival hyperplasia syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function FA20A_HUMAN Pseudokinase that acts as an allosteric activator of the Golgi serine/threonine protein kinase FAM20C and is involved in biomineralization of teeth. Forms a complex with FAM20C and increases the ability of FAM20C to phosphorylate the proteins that form the 'matrix' that guides the deposition of the enamel minerals. Publication Abstract from PubMed The Fam20 proteins are novel kinases that phosphorylate secreted proteins and proteoglycans. Fam20C phosphorylates hundreds of secreted proteins and is activated by the pseudokinase Fam20A. Fam20B phosphorylates a xylose residue to regulate proteoglycan synthesis. Despite these wide-ranging and important functions, the molecular and structural basis for the regulation and substrate specificity of these kinases are unknown. Here we report molecular characterizations of all three Fam20 kinases, and show that Fam20C is activated by the formation of an evolutionarily conserved homodimer or heterodimer with Fam20A. Fam20B has a unique active site for recognizing Galbeta1-4Xylbeta1, the initiator disaccharide within the tetrasaccharide linker region of proteoglycans. We further show that in animals the monomeric Fam20B preceded the appearance of the dimeric Fam20C, and the dimerization trait of Fam20C emerged concomitantly with a change in substrate specificity. Our results provide comprehensive structural, biochemical, and evolutionary insights into the function of the Fam20 kinases. Structure and evolution of the Fam20 kinases.,Zhang H, Zhu Q, Cui J, Wang Y, Chen MJ, Guo X, Tagliabracci VS, Dixon JE, Xiao J Nat Commun. 2018 Mar 23;9(1):1218. doi: 10.1038/s41467-018-03615-z. PMID:29572475 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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