PDBsum entry 2yx8

Protein transport

PDB id: 2yx8

Contents

Protein chain

81 a.a. *

Waters ×17

* Residue conservation analysis

PDB id:

2yx8

Name:

Protein transport

Title:

Crystal structure of the extracellular domain of human ramp1

Structure:

Receptor activity-modifying protein 1. Chain: a. Fragment: extracellular domain. Synonym: crlr activity- modifying protein 1, calcitonin-receptor-like receptor activity- modifying protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ramp1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.40Å R-factor: 0.221 R-free: 0.281

Authors:

S.Kusano,M.Kukimoto-Niino,M.Shirouzu,T.Shindo,S.Yokoyama,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

S.Kusano et al. (2008). Crystal structure of the human receptor activity-modifying protein 1 extracellular domain. Protein Sci, 17, 1907-1914. PubMed id: 18725456 DOI: 10.1110/ps.036012.108

Date:

24-Apr-07 Release date: 29-Apr-08

Protein chain

O60894  (RAMP1_HUMAN) -  Receptor activity-modifying protein 1 from Homo sapiens

Seq: 148 a.a.

Struc: 81 a.a.

DOI no: 10.1110/ps.036012.108

Protein Sci 17:1907-1914 (2008)

PubMed id: 18725456

Crystal structure of the human receptor activity-modifying protein 1 extracellular domain.

S.Kusano, M.Kukimoto-Niino, R.Akasaka, M.Toyama, T.Terada, M.Shirouzu, T.Shindo, S.Yokoyama.

ABSTRACT

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.

Selected figure(s)

Figure 3.
Structural features of the molecular surface of RAMP1. (A) Ribbon representation of RAMP1. The two views are related by a 180[deg] rotation about the vertical axis. The three disulfide bonds are shown in yellow. (B) Blue and red surfaces represent positive and negative potentials, respectively. The molecular orientations in B, C, and D are the same as in A. The circle indicates the location of the hydrophobic patch, which exists in the shallow concave area between [alpha]2 and [alpha]3. (C) Residue conservation mapping on the surface of RAMP1. Red and orange surfaces indicate the locations of identical and similar residues among human RAMPs, respectively, according to the sequence alignment in Figure 1A Figure 1.-. (D) Mapping of the binding-site residues on the RAMP1 surface. Residues Phe93, His97, Tyr101, which are reportedly important for the formation of the RAMP1[center dot]CRLR interaction (Kuwasako et al. 2001, 2003; Simms et al. 2006), are colored pink. Trp74, which was previously identified as the high-affinity binding site of the nonpeptide antagonist BIBN4096BS (Doods et al. 2000; Mallee et al. 2002), is colored cyan. Leu94, which when replaced by alanine reportedly caused a great increase in cell-surface expression and CRLR binding, is colored yellow.

Figure 4.
View of the putative RAMP1 interface region with CRLR. Selected residues in Figure 3D Figure 3.-are labeled. Note that among the residues that are reportedly important for the formation of the RAMP1[center dot]CRLR interface (pink), the side chains of Phe93 and Tyr101 point toward the inside of the molecule, while that of His97 points toward the outside the molecule.

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2008, 17, 1907-1914) copyright 2008.

Figures were selected by an automated process.