Document Detail

The interaction with the cytoplasmic loops of rhodopsin plays a crucial role in arrestin activation and binding.
MedLine Citation:
PMID:  12603828     Owner:  NLM     Status:  MEDLINE    
The binding of arrestin to rhodopsin is initiated by the interaction of arrestin with the phosphorylated rhodopsin C-terminus and/or the cytoplasmic loops, followed by conformational changes that expose an additional high-affinity site on arrestin. Here we use an arrestin mutant (R175E) that binds similarly to phosphorylated and unphosphorylated, wild-type rhodopsin to identify rhodopsin elements other than C-terminus important for arrestin interaction. R175E-arrestin demonstrated greatly reduced binding to unphosphorylated cytoplasmic loop mutants L72A, N73A, P142A and M143A, suggesting that these residues are crucial for high-affinity binding. Interestingly, when these rhodopsin mutants are phosphorylated, R175E-arrestin binding is less severely affected. This effect of phosphorylation on R175E-arrestin binding highlights the co-operative nature of the multi-site interaction between arrestin and the cytoplasmic loops and C-terminus of rhodopsin. However, a combination of any two mutations disrupts the ability of phosphorylation to enhance binding of R175E-arrestin. N73A, P142A and M143A exhibited accelerated rates of dissociation from wild-type arrestin. Using sensitivity to calpain II as an assay, these cytoplasmic loop mutants also demonstrated reduced ability to induce conformational changes in arrestin that correlated with their reduced ability to bind arrestin. These results suggest that arrestin bound to rhodopsin is in a distinct conformation that is co-ordinately regulated by association with the cytoplasmic loops and the C-terminus of rhodopsin.
Dayanidhi Raman; Shoji Osawa; Vsevolod V Gurevich; Ellen R Weiss
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  84     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-02-26     Completed Date:  2003-03-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1040-50     Citation Subset:  IM    
Department of Cell and Developmental Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7090, USA.
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MeSH Terms
Amino Acid Substitution
Arrestin / chemistry*,  genetics,  metabolism*
Calpain / chemistry
Mutagenesis, Site-Directed
Protein Binding / physiology
Protein Conformation
Protein Structure, Tertiary / physiology
Rhodopsin / chemistry*,  genetics,  metabolism*
Structure-Activity Relationship
Grant Support
Reg. No./Substance:
0/Arrestin; 9009-81-8/Rhodopsin; EC 3.4.22.-/Calpain

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

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