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2qa7

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2qa7, resolution 2.80Å ()
Gene: HIP1 (Homo sapiens)
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Crystal structure of Huntingtin-interacting protein 1 (HIP1) coiled-coil domain with a basic surface suitable for HIP-protein interactor (HIPPI)

Publication Abstract from PubMed

Huntington's disease is a genetic neurological disorder that is triggered by the dissociation of the huntingtin protein (htt) from its obligate interaction partner Huntingtin-interacting protein 1 (HIP1). The release of the huntingtin protein permits HIP1 protein interactor (HIPPI) to bind to its recognition site on HIP1 to form a HIPPI/HIP1 complex that recruits procaspase-8 to begin the process of apoptosis. The interaction module between HIPPI and HIP1 was predicted to resemble a death-effector domain. Our 2.8-A crystal structure of the HIP1 371-481 subfragment that includes F432 and K474, which is important for HIPPI binding, is not a death-effector domain but is a partially opened coiled coil. The HIP1 371-481 model reveals a basic surface that we hypothesize to be suitable for binding HIPPI. There is an opened region next to the putative HIPPI site that is highly negatively charged. The acidic residues in this region are highly conserved in HIP1 and a related protein, HIP1R, from different organisms but are not conserved in the yeast homologue of HIP1, sla2p. We have modeled approximately 85% of the coiled-coil domain by joining our new HIP1 371-481 structure to the HIP1 482-586 model (Protein Data Bank code: 2NO2). Finally, the middle of this coiled-coil domain may be intrinsically flexible and suggests a new interaction model where HIPPI binds to a U-shaped HIP1 molecule.

Crystal structure at 2.8 A of Huntingtin-interacting protein 1 (HIP1) coiled-coil domain reveals a charged surface suitable for HIP1 protein interactor (HIPPI)., Niu Q, Ybe JA, J Mol Biol. 2008 Feb 1;375(5):1197-205. Epub 2007 Nov 22. PMID:18155047

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2QA7 is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Niu Q, Ybe JA. Crystal structure at 2.8 A of Huntingtin-interacting protein 1 (HIP1) coiled-coil domain reveals a charged surface suitable for HIP1 protein interactor (HIPPI). J Mol Biol. 2008 Feb 1;375(5):1197-205. Epub 2007 Nov 22. PMID:18155047 doi:10.1016/j.jmb.2007.11.036

Page seeded by OCA on Mon Feb 16 15:08:28 2009

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