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Title: Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain

Abstract

Variable packing interaction related to the conformational flexibility within the huntingtin-interacting protein 1 coiled coil domain. Huntingtin-interacting protein 1 (HIP1) is an important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery. HIP1 has also been implicated in the pathogenesis of Huntington’s disease. The binding of HIP1 to actin is regulated through an interaction with clathrin light chain. Clathrin light chain binds to a flexible coiled-coil domain in HIP1 and induces a compact state that is refractory to actin binding. To understand the mechanism of this conformational regulation, a high-resolution crystal structure of a stable fragment from the HIP1 coiled-coil domain was determined. The flexibility of the HIP1 coiled-coil region was evident from its variation from a previously determined structure of a similar region. A hydrogen-bond network and changes in coiled-coil monomer interaction suggest that the HIP1 coiled-coil domain is uniquely suited to allow conformational flexibility.

Authors:
 [1];  [2];  [1]
  1. Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143 (United States)
  2. The G. W. Hooper Foundation, Departments of Microbiology and Immunology and of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California 94143 (United States)
Publication Date:
OSTI Identifier:
22351203
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section D: Biological Crystallography
Additional Journal Information:
Journal Volume: 66; Journal Issue: Pt 3; Other Information: PMCID: PMC2827350; PMID: 20179344; PUBLISHER-ID: mh5028; OAI: oai:pubmedcentral.nih.gov:2827350; Copyright (c) International Union of Crystallography 2010; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0907-4449
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; COMPACTS; CRYSTAL STRUCTURE; FLEXIBILITY; HYDROGEN; INTERACTIONS; MONOMERS; RESOLUTION; STOWING; VARIATIONS; VISIBLE RADIATION

Citation Formats

Wilbur, Jeremy D., E-mail: jwilbur@msg.ucsf.edu, Hwang, Peter K., Brodsky, Frances M., Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, Fletterick, Robert J., Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, and Graduate Program in Biophysics, University of California, San Francisco, California 94143. Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain. Denmark: N. p., 2010. Web. doi:10.1107/S0907444909054535.
Wilbur, Jeremy D., E-mail: jwilbur@msg.ucsf.edu, Hwang, Peter K., Brodsky, Frances M., Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, Fletterick, Robert J., Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, & Graduate Program in Biophysics, University of California, San Francisco, California 94143. Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain. Denmark. https://doi.org/10.1107/S0907444909054535
Wilbur, Jeremy D., E-mail: jwilbur@msg.ucsf.edu, Hwang, Peter K., Brodsky, Frances M., Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, Fletterick, Robert J., Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143, and Graduate Program in Biophysics, University of California, San Francisco, California 94143. 2010. "Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain". Denmark. https://doi.org/10.1107/S0907444909054535.
@article{osti_22351203,
title = {Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain},
author = {Wilbur, Jeremy D., E-mail: jwilbur@msg.ucsf.edu and Hwang, Peter K. and Brodsky, Frances M. and Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143 and Fletterick, Robert J. and Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143 and Graduate Program in Biophysics, University of California, San Francisco, California 94143},
abstractNote = {Variable packing interaction related to the conformational flexibility within the huntingtin-interacting protein 1 coiled coil domain. Huntingtin-interacting protein 1 (HIP1) is an important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery. HIP1 has also been implicated in the pathogenesis of Huntington’s disease. The binding of HIP1 to actin is regulated through an interaction with clathrin light chain. Clathrin light chain binds to a flexible coiled-coil domain in HIP1 and induces a compact state that is refractory to actin binding. To understand the mechanism of this conformational regulation, a high-resolution crystal structure of a stable fragment from the HIP1 coiled-coil domain was determined. The flexibility of the HIP1 coiled-coil region was evident from its variation from a previously determined structure of a similar region. A hydrogen-bond network and changes in coiled-coil monomer interaction suggest that the HIP1 coiled-coil domain is uniquely suited to allow conformational flexibility.},
doi = {10.1107/S0907444909054535},
url = {https://www.osti.gov/biblio/22351203}, journal = {Acta Crystallographica. Section D: Biological Crystallography},
issn = {0907-4449},
number = Pt 3,
volume = 66,
place = {Denmark},
year = {Mon Mar 01 00:00:00 EST 2010},
month = {Mon Mar 01 00:00:00 EST 2010}
}