2wfq

Crystal structure of the N-terminal signalling domain of human Dhh without calcium

spinqualitylabelsall models 2wfq, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wfq 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 1.85Å Ligands: SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease DHH_HUMAN Defects in DHH may be the cause of partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:607080. PGD is characterized by the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity. Defects in DHH may be the cause of complete pure gonadal dysgenesis 46,XY type (GDXYM) [MIM:233420; also known as male-limited gonadal dysgenesis 46,XY. GDXYM is a type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be non-functional streaks. Function DHH_HUMAN Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Hedgehog (Hh) morphogens have fundamental roles in development, whereas dysregulation of Hh signaling leads to disease. Multiple cell-surface receptors are responsible for transducing and/or regulating Hh signals. Among these, the Hedgehog-interacting protein (Hhip) is a highly conserved, vertebrate-specific inhibitor of Hh signaling. We have solved a series of crystal structures for the human HHIP ectodomain and Desert hedgehog (DHH) in isolation, as well as HHIP in complex with DHH (HHIP-DHH) and Sonic hedgehog (Shh) (HHIP-Shh), with and without Ca2+. The interaction determinants, confirmed by biophysical studies and mutagenesis, reveal previously uncharacterized and distinct functions for the Hh Zn2+ and Ca2+ binding sites--functions that may be common to all vertebrate Hh proteins. Zn2+ makes a key contribution to the Hh-HHIP interface, whereas Ca2+ is likely to prevent electrostatic repulsion between the two proteins, suggesting an important modulatory role. This interplay of several metal binding sites suggests a tuneable mechanism for regulation of Hh signaling. Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP.,Bishop B, Aricescu AR, Harlos K, O'Callaghan CA, Jones EY, Siebold C Nat Struct Mol Biol. 2009 Jul;16(7):698-703. Epub 2009 Jun 28. PMID:19561611 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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