scholarly journals Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain

2010 ◽  
Vol 66 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Jeremy D. Wilbur ◽  
Peter K. Hwang ◽  
Frances M. Brodsky ◽  
Robert J. Fletterick
Keyword(s):  
Light Chain ◽  
Coiled Coil ◽  
Actin Binding ◽  
Interacting Protein ◽  
Similar Region ◽  
Coiled Coil Domain ◽  
Coiled Coil Region ◽  
Huntingtin Interacting Protein 1 ◽  
Conformational Regulation ◽  
Huntingtin Interacting Protein

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.

scholarly journals Actin Binding by Hip1 (Huntingtin-interacting Protein 1) and Hip1R (Hip1-related Protein) Is Regulated by Clathrin Light Chain

2008 ◽  
Vol 283 (47) ◽  
pp. 32870-32879 ◽  
Author(s):  
Jeremy D. Wilbur ◽  
Chih-Ying Chen ◽  
Venus Manalo ◽  
Peter K. Hwang ◽  
Robert J. Fletterick ◽  
...  
Keyword(s):  
Light Chain ◽  
Actin Binding ◽  
Related Protein ◽  
Interacting Protein ◽  
Huntingtin Interacting Protein 1 ◽  
Huntingtin Interacting Protein

scholarly journals Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors

2005 ◽  
Vol 170 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Ian G. Mills ◽  
Luke Gaughan ◽  
Craig Robson ◽  
Theodora Ross ◽  
Stuart McCracken ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Hormone Receptors ◽  
Nuclear Translocation ◽  
Coiled Coil ◽  
Adaptor Proteins ◽  
Cellular Transformation ◽  
Interacting Protein ◽  
Response Elements ◽  
Huntingtin Interacting Protein 1 ◽  
Huntingtin Interacting Protein

Internalization of activated receptors regulates signaling, and endocytic adaptor proteins are well-characterized in clathrin-mediated uptake. One of these adaptor proteins, huntingtin interacting protein 1 (HIP1), induces cellular transformation and is overexpressed in some prostate cancers. We have discovered that HIP1 associates with the androgen receptor through a central coiled coil domain and is recruited to DNA response elements upon androgen stimulation. HIP1 is a novel androgen receptor regulator, significantly repressing transcription when knocked down using a silencing RNA approach and activating transcription when overexpressed. We have also identified a functional nuclear localization signal at the COOH terminus of HIP1, which contributes to the nuclear translocation of the protein. In conclusion, we have discovered that HIP1 is a nucleocytoplasmic protein capable of associating with membranes and DNA response elements and regulating transcription.

scholarly journals Clathrin binding to the DLLRKN region of Huntingtin‐interacting protein 1 (HIP1) requires coiled coil instability

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Joel Alcasid Ybe ◽  
Arun Alphonse Ignatius ◽  
David Giedroc ◽  
Melissa Illingworth ◽  
Sara Poorfarahani
Keyword(s):  
Coiled Coil ◽  
Interacting Protein ◽  
Huntingtin Interacting Protein 1 ◽  
Huntingtin Interacting Protein

scholarly journals Huntingtin Interacting Protein 1 (HIP1) Regulates Clathrin Assembly through Direct Binding to the Regulatory Region of the Clathrin Light Chain

2004 ◽  
Vol 280 (7) ◽  
pp. 6101-6108 ◽  
Author(s):  
Valerie Legendre-Guillemin ◽  
Martina Metzler ◽  
Jean-Francois Lemaire ◽  
Jacynthe Philie ◽  
Lu Gan ◽  
...  
Keyword(s):  
Light Chain ◽  
Regulatory Region ◽  
Interacting Protein ◽  
Direct Binding ◽  
Huntingtin Interacting Protein 1 ◽  
Huntingtin Interacting Protein

scholarly journals Two Distantly Spaced Basic Patches in the Flexible Domain of Huntingtin-Interacting Protein 1 (HIP1) Are Essential for the Binding of Clathrin Light Chain

2009 ◽  
Vol 2009 ◽  
pp. 1-5
Author(s):  
Joel A. Ybe ◽  
Mary E. Clegg ◽  
Melissa Illingworth ◽  
Claire Gonzalez ◽  
Qian Niu
Keyword(s):  
Binding Site ◽  
Light Chain ◽  
Low Temperatures ◽  
Structural Unit ◽  
Interacting Protein ◽  
C Elegans ◽  
Huntingtin Interacting Protein 1 ◽  
The Stability ◽  
Huntingtin Interacting Protein ◽  
Circular Dichroïsm

The interaction between HIP family proteins (HIP1 and HIP12/1R) and clathrin is fundamental to endocytosis. We used circular dichroism (CD) to study the stability of an HIP1 subfragment (aa468-530) that is splayed open. CD thermal melts show HIP1 468-530 is only stable at low temperatures, but this HIP1 fragment contains a structural unit that does not melt out even at 83C∘. We then created HIP1 mutants to probe our hypothesis that a short hydrophobic path in the opened region is the binding site for clathrin light chain. We found that the binding of hub/LCb was sensitive to mutating two distantly separated basic residues (K474 and K494). The basic patches marked by K474 and K494 are conserved in HIP12/1R. The lack of conservation insla2p (S. cerevisiae), HIP1 fromD. melanogaster, and HIP1 homolog ZK370.3 fromC. elegansimplies the binding of HIP1 and HIP1 homologs to clathrin light chain may be different in these organisms.

scholarly journals Huntingtin Interacting Protein 1 Is a Clathrin Coat Binding Protein Required for Differentiation of late Spermatogenic Progenitors

2001 ◽  
Vol 21 (22) ◽  
pp. 7796-7806 ◽  
Author(s):  
Dinesh S. Rao ◽  
Jenny C. Chang ◽  
Priti D. Kumar ◽  
Ikuko Mizukami ◽  
Glennda M. Smithson ◽  
...  
Keyword(s):  
Leucine Zipper ◽  
Actin Binding ◽  
Seminiferous Tubules ◽  
First Year ◽  
Interacting Protein ◽  
Normal Peripheral Blood ◽  
Huntingtin Interacting Protein 1 ◽  
Β Receptor ◽  
First Year Of Life ◽  
Huntingtin Interacting Protein

ABSTRACT Huntingtin-interacting protein 1 (HIP1) interacts with huntingtin, the protein whose gene is mutated in Huntington's disease. In addition, a fusion between HIP1 and platelet-derived growth factor β receptor causes chronic myelomonocytic leukemia. The HIP1 proteins, including HIP1 and HIP1-related (HIP1r), have an N-terminal polyphosphoinositide-interacting epsin N-terminal homology, domain, which is found in proteins involved in clathrin-mediated endocytosis. HIP1 and HIP1r also share a central leucine zipper and an actin binding TALIN homology domain. Here we show that HIP1, like HIP1r, colocalizes with clathrin coat components. We also show that HIP1 physically associates with clathrin and AP-2, the major components of the clathrin coat. To further understand the putative biological role(s) ofHIP1, we have generated a targeted deletion of murineHIP1. HIP1 −/− mice developed into adulthood, did not develop overt neurologic symptoms in the first year of life, and had normal peripheral blood counts. However, HIP1-deficient mice exhibited testicular degeneration with increased apoptosis of postmeiotic spermatids. Postmeiotic spermatids are the only cells of the seminiferous tubules that express HIP1. These findings indicate that HIP1 is required for differentiation, proliferation, and/or survival of spermatogenic progenitors. The association of HIP1 with clathrin coats and the requirement of HIP1 for progenitor survival suggest a role for HIP1 in the regulation of endocytosis.

scholarly journals An Actin-Binding Protein of the Sla2/Huntingtin Interacting Protein 1 Family Is a Novel Component of Clathrin-Coated Pits and Vesicles

1999 ◽  
Vol 147 (7) ◽  
pp. 1503-1518 ◽  
Author(s):  
Åsa E.Y. Engqvist-Goldstein ◽  
Michael M. Kessels ◽  
Vikramjit S. Chopra ◽  
Michael R. Hayden ◽  
David G. Drubin
Keyword(s):  
Actin Cytoskeleton ◽  
Binding Protein ◽  
Actin Binding ◽  
Cell Cortex ◽  
Sequence Alignments ◽  
Coated Pits ◽  
Interacting Protein ◽  
Actin Binding Protein ◽  
Huntingtin Interacting Protein 1 ◽  
Huntingtin Interacting Protein

The actin cytoskeleton has been implicated in endocytosis, yet few molecules that link these systems have been identified. Here, we have cloned and characterized mHip1R, a protein that is closely related to huntingtin interacting protein 1 (Hip1). These two proteins are mammalian homologues of Sla2p, an actin binding protein important for actin organization and endocytosis in yeast. Sequence alignments and secondary structure predictions verified that mHip1R belongs to the Sla2 protein family. Thus, mHip1R contains an NH2-terminal domain homologous to that implicated in Sla2p's endocytic function, three predicted coiled–coils, a leucine zipper, and a talin-like actin-binding domain at the COOH terminus. The talin-like domain of mHip1R binds to F-actin in vitro and colocalizes with F-actin in vivo, indicating that this activity has been conserved from yeast to mammals. mHip1R shows a punctate immunolocalization and is enriched at the cell cortex and in the perinuclear region. We concluded that the cortical localization represents endocytic compartments, because mHip1R colocalizes with clathrin, AP-2, and endocytosed transferrin, and because mHip1R fractionates biochemically with clathrin-coated vesicles. Time-lapse video microscopy of mHip1R–green fluorescence protein (GFP) revealed a blinking behavior similar to that reported for GFP-clathrin, and an actin-dependent inward movement of punctate structures from the cell periphery. These data show that mHip1R is a component of clathrin-coated pits and vesicles and suggest that it might link the endocytic machinery to the actin cytoskeleton.

Lamellipodial localization ofDictyosteliummyosin heavy chain kinase A is mediated via F-actin binding by the coiled-coil domain

FEBS Letters ◽  
2002 ◽  
Vol 516 (1-3) ◽  
pp. 58-62 ◽  
Author(s):  
Paul A Steimle ◽  
Lucila Licate ◽  
Graham P Côté ◽  
Thomas T Egelhoff
Keyword(s):  
Heavy Chain ◽  
Coiled Coil ◽  
Actin Binding ◽  
Coiled Coil Domain ◽  
Kinase A
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