2WFR

Crystal structure of the N-terminal signalling domain of human Dhh with calcium

2WFR の概要

• エントリーDOI: 10.2210/pdb2wfr/pdb
• 関連するPDBエントリー: 2WFQ 2WFT 2WFX 2WG3 2WG4
• 分子名称: DESERT HEDGEHOG PROTEIN N-PRODUCT, ZINC ION, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: lipoprotein, development, cell membrane, autocatalytic cleavage, signaling protein, disease mutation, hedgehog signalling, protease, membrane, secreted, palmitate, hydrolase, signal transduction, developmental protein
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19186.77

構造登録者

Bishop, B.,Aricescu, A.R.,Harlos, K.,O'Callaghan, C.A.,Jones, E.Y.,Siebold, C. (登録日: 2009-04-14, 公開日: 2009-06-30, 最終更新日: 2023-12-13)

主引用文献

Bishop, B.,Aricescu, A.R.,Harlos, K.,O'Callaghan, C.A.,Jones, E.Y.,Siebold, C.
Structural Insights Into Hedgehog Ligand Sequestration by the Human Hedgehog-Interacting Protein Hip
Nat.Struct.Mol.Biol., 16:698-, 2009

PubMed Abstract: 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.

PubMed: 19561611
DOI: 10.1038/NSMB.1607

実験手法

X-RAY DIFFRACTION (1.95 Å)