3HO4

Crystal structure of Hedgehog-interacting protein (HHIP)

3HO4 の概要

• エントリーDOI: 10.2210/pdb3ho4/pdb
• 関連するPDBエントリー: 3HO3 3HO5
• 分子名称: Hedgehog-interacting protein (1 entity in total)
• 機能のキーワード: receptor ectodomain, six-bladed-propeller domain, egf domain, disulfide bond, cell membrane, egf-like domain, glycoprotein, membrane, secreted, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Peripheral membrane protein (By similarity). Isoform 2: Cytoplasm (Probable): Q96QV1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 108831.02

構造登録者

Hymowitz, S.G.,Bosanac, I. (登録日: 2009-06-01, 公開日: 2009-06-23, 最終更新日: 2024-10-16)

主引用文献

Bosanac, I.,Maun, H.R.,Scales, S.J.,Wen, X.,Lingel, A.,Bazan, J.F.,de Sauvage, F.J.,Hymowitz, S.G.,Lazarus, R.A.
The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling.
Nat.Struct.Mol.Biol., 16:691-697, 2009

PubMed Abstract: Hedgehog (Hh) signaling is crucial for many aspects of embryonic development, whereas dysregulation of this pathway is associated with several types of cancer. Hedgehog-interacting protein (Hhip) is a surface receptor antagonist that is equipotent against all three mammalian Hh homologs. The crystal structures of human HHIP alone and bound to Sonic hedgehog (SHH) now reveal that HHIP is comprised of two EGF domains and a six-bladed beta-propeller domain. In the complex structure, a critical loop from HHIP binds the pseudo active site groove of SHH and directly coordinates its Zn2+ cation. Notably, sequence comparisons of this SHH binding loop with the Hh receptor Patched (Ptc1) ectodomains and HHIP- and PTC1-peptide binding studies suggest a 'patch for Patched' at the Shh pseudo active site; thus, we propose a role for Hhip as a structural decoy receptor for vertebrate Hh.

PubMed: 19561609
DOI: 10.1038/nsmb.1632

実験手法

X-RAY DIFFRACTION (3.1 Å)