Identification of cholesterol recognition amino acid consensus (CRAC) motif in G-protein coupled receptors

Jafurulla, Md. ; Tiwari, Shrish ; Chattopadhyay, Amitabha (2011) Identification of cholesterol recognition amino acid consensus (CRAC) motif in G-protein coupled receptors Biochemical and Biophysical Research Communications, 404 (1). pp. 569-573. ISSN 0006-291X

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Related URL: http://dx.doi.org/10.1016/j.bbrc.2010.12.031

Abstract

G-protein coupled receptors (GPCRs) are the largest class of molecules involved in signal transduction across membranes, and represent major targets in the development of novel drug candidates in all clinical areas. Membrane cholesterol has been reported to have an important role in the function of a number of GPCRs. Several structural features of proteins, believed to result in preferential association with cholesterol, have been recognized. Cholesterol recognition/interaction amino acid consensus (CRAC) sequence represents such a motif. Many proteins that interact with cholesterol have been shown to contain the CRAC motif in their sequence. We report here the presence of CRAC motifs in three representative GPCRs, namely, rhodopsin, the β2-adrenergic receptor, and the serotonin1A receptor. Interestingly, the function of these GPCRs has been previously shown to be dependent on membrane cholesterol. The presence of CRAC motifs in GPCRs indicates that interaction of cholesterol with GPCRs could be specific in nature. Further analysis shows that CRAC motifs are inherent characteristic features of the serotonin1A receptor and are conserved over natural evolution. These results constitute the first report of the presence of CRAC motifs in GPCRs and provide novel insight in the molecular nature of GPCR-cholesterol interaction.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:CRAC; Cholesterol; GPCR; Serotonin1A Receptor; Specific Interaction
ID Code:85733
Deposited On:05 Mar 2012 13:32
Last Modified:05 Mar 2012 13:32

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