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

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.

2008 ◽  
Vol 283 (47) ◽  
pp. 32870-32879 ◽  
Author(s):  
Jeremy D. Wilbur ◽  
Chih-Ying Chen ◽  
Venus Manalo ◽  
Peter K. Hwang ◽  
Robert J. Fletterick ◽  
...  

2010 ◽  
Vol 66 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Jeremy D. Wilbur ◽  
Peter K. Hwang ◽  
Frances M. Brodsky ◽  
Robert J. Fletterick

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.


2004 ◽  
Vol 280 (7) ◽  
pp. 6101-6108 ◽  
Author(s):  
Valerie Legendre-Guillemin ◽  
Martina Metzler ◽  
Jean-Francois Lemaire ◽  
Jacynthe Philie ◽  
Lu Gan ◽  
...  

2000 ◽  
Vol 275 (52) ◽  
pp. 41299-41308 ◽  
Author(s):  
Abigail S. Hackam ◽  
Ayman S. Yassa ◽  
Roshni Singaraja ◽  
Martina Metzler ◽  
Claire-Anne Gutekunst ◽  
...  

2007 ◽  
Vol 67 (18) ◽  
pp. 8923-8931 ◽  
Author(s):  
Sarah V. Bradley ◽  
Mitchell R. Smith ◽  
Teresa S. Hyun ◽  
Peter C. Lucas ◽  
Lina Li ◽  
...  

2008 ◽  
Vol 28 (3) ◽  
pp. 599-609 ◽  
Author(s):  
Justin N. Moores ◽  
Sophie Roy ◽  
Donald W. Nicholson ◽  
Brian E. Staveley

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