title: Crystal structure at 2.8 A of the DLLRKN-containing coiled-coil domain of huntingtin-interacting protein 1 (HIP1) reveals a surface suitable for clathrin light chain binding.
abstract: Huntingtin interacting protein 1 (HIP1) is a member of a family of proteins whose interaction with Huntingtin is critical to prevent cells from initiating apoptosis. HIP1, and related protein HIP12/1R, can also bind to clathrin and membrane phospholipids, and HIP12/1R links the CCV to the actin cytoskeleton. HIP1 and HIP12/1R interact with the clathrin light chain EED regulatory site and stimulate clathrin lattice assembly. Here, we report the X-ray structure of the coiled-coil domain of HIP1 (residues 482-586) that includes residues crucial for binding clathrin light chain. The dimeric HIP1 crystal structure is partially splayed open. The comparison of the HIP1 model with coiled-coil predictions revealed the heptad repeat in the dimeric trunk (S2 path) is offset relative to the register of the heptad repeat from the N-terminal portion (S1 path) of the molecule. Furthermore, surface analysis showed there is a third hydrophobic path (S3) running parallel with S1 and S2. We present structural evidence supporting a role for the S3 path as an interaction surface for clathrin light chain. Finally, comparative analysis suggests the mode of binding between sla2p and clathrin light chain may be different in yeast.
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Ybe
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mishra
authors.forename: Stephen
authors.initials: S
authors.lastname: Helms
authors.forename: Jay
authors.initials: J
authors.lastname: Nix
mesh_terms: D001665:Binding Sites; D033941:Clathrin Light Chains / Q000378:metabolism*; D017124:Conserved Sequence; D003460:Crystallization; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014961:X-Ray Diffraction
chemical_list: D033941:Clathrin Light Chains; D004268:DNA-Binding Proteins; C073368:HIP1 protein, human; D010455:Peptides