3HO5

Crystal structure of Hedgehog-interacting protein (HHIP) and Sonic hedgehog (SHH) complex

Summary for 3HO5

• Entry DOI: 10.2210/pdb3ho5/pdb
• Related: 3HO3 3HO4
• Descriptor: Hedgehog-interacting protein, Sonic hedgehog protein, ZINC ION, ... (4 entities in total)
• Functional Keywords: receptor ectodomain, six-bladed-propeller domain, egf domain, disulfide bond, calcium cation, zinc cation, cell membrane, egf-like domain, glycoprotein, membrane, secreted, autocatalytic cleavage, developmental protein, disease mutation, holoprosencephaly, hydrolase, lipoprotein, microphthalmia, palmitate, protease, signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Peripheral membrane protein (By similarity). Isoform 2: Cytoplasm (Probable): Q96QV1; Sonic hedgehog protein C-product: Secreted, extracellular space (By similarity). Sonic hedgehog protein N-product: Cell membrane; Lipid-anchor (By similarity): Q15465
• Total number of polymer chains: 3
• Total formula weight: 127507.95

Authors

Hymowitz, S.G.,Bosanac, I. (deposition date: 2009-06-01, release date: 2009-06-23, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.01 Å)