HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article ACCEPTED PREPRINT Full Text (PDF) All Versions of this Article: ps.036012.108v1 17/11/1907    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kusano, S. Articles by Yokoyama, S. PubMed PubMed Citation Articles by Kusano, S. Articles by Yokoyama, S. Social Bookmarking                   What's this?

Crystal Structure of the Human Receptor Activity-Modifying Protein 1 Extracellular Domain

¹ Systems and Structural Biology Center, Yokohama Institute, RIKEN;
² Graduate School of Medicine, Shinshu University

(RECEIVED April 25, 2008; ACCEPTED August 15, 2008)

Receptor activity-modifying protein (RAMP) 1 forms a heterodimer with calcitonin receptor-like receptor (CRLR) and regulates its transport to the cell surface. The CRLR·RAMP1 heterodimer functions as a specific receptor for calcitonin gene-related peptide (CGRP). Here, we report the crystal structure of the human RAMP1 extracellular domain. The RAMP1 structure is a three-helix bundle that is stabilized by three disulfide bonds. The RAMP1 residues important for cell-surface expression of the CRLR·RAMP1 heterodimer are clustered to form a hydrophobic patch on the molecular surface. The hydrophobic patch is located near the tryptophan residue essential for binding of the CGRP antagonist, BIBN4096BS. These results suggest that the hydrophobic patch participates in the interaction with CRLR and the formation of the ligand-binding pocket when it forms the CRLR·RAMP1 heterodimer.

Keywords: Adrenomedullin; CGRP; CRLR; GPCR; Physiological activating peptide; X-ray crystallography

³ E-mail: yokoyama{at}biochem.s.u-tokyo.ac.jp

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?