4wrn | pdb_00004wrn

Crystal structure of the polymerization region of human uromodulin/Tamm-Horsfall protein

spinqualitylabelsall models 4wrn, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4wrn is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MAL, NAG, ZN Related: 3d4g, 3nk4, 5bup Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MALE_ECO57] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides (By similarity). Publication Abstract from PubMed Uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant human urinary protein, plays a key role in chronic kidney diseases and is a promising therapeutic target for hypertension. Via its bipartite zona pellucida module (ZP-N/ZP-C), UMOD forms extracellular filaments that regulate kidney electrolyte balance and innate immunity, as well as protect against renal stones. Moreover, salt-dependent aggregation of UMOD filaments in the urine generates a soluble molecular net that captures uropathogenic bacteria and facilitates their clearance. Despite the functional importance of its homopolymers, no structural information is available on UMOD and how it self-assembles into filaments. Here, we report the crystal structures of polymerization regions of human UMOD and mouse ZP2, an essential sperm receptor protein that is structurally related to UMOD but forms heteropolymers. The structure of UMOD reveals that an extensive hydrophobic interface mediates ZP-N domain homodimerization. This arrangement is required for filament formation and is directed by an ordered ZP-N/ZP-C linker that is not observed in ZP2 but is conserved in the sequence of deafness/Crohn's disease-associated homopolymeric glycoproteins alpha-tectorin (TECTA) and glycoprotein 2 (GP2). Our data provide an example of how interdomain linker plasticity can modulate the function of structurally similar multidomain proteins. Moreover, the architecture of UMOD rationalizes numerous pathogenic mutations in both UMOD and TECTA genes. A structured interdomain linker directs self-polymerization of human uromodulin.,Bokhove M, Nishimura K, Brunati M, Han L, de Sanctis D, Rampoldi L, Jovine L Proc Natl Acad Sci U S A. 2016 Jan 25. pii: 201519803. PMID:26811476 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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