3AQE

Crystal structure of the extracellular domain of human RAMP2

Summary for 3AQE

• Entry DOI: 10.2210/pdb3aqe/pdb
• Related: 3AQF
• Descriptor: Receptor activity-modifying protein 2 (2 entities in total)
• Functional Keywords: transmembrane, gpcr, adrenomedullin, trafficking, clr, cgrp, endoplasmic reticulum, disease, neovascularization, helix bundle, calcitonin receptor-like receptor (crlr), endoplasmic reticulum (er), cell membrane, transport protein
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: O60895
• Total number of polymer chains: 6
• Total formula weight: 63488.83

Authors

Kusano, S.,Kukimoto-Niino, M.,Shirouzu, M.,Shindo, T.,Yokoyama, S. (deposition date: 2010-10-29, release date: 2011-11-09, Last modification date: 2024-10-09)

Primary citation

Kusano, S.,Kukimoto-Niino, M.,Hino, N.,Ohsawa, N.,Okuda, K.,Sakamoto, K.,Shirouzu, M.,Shindo, T.,Yokoyama, S.
Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding
Protein Sci., 21:199-210, 2012

PubMed Abstract: The calcitonin receptor-like receptor (CRLR), a class B GPCR, forms a heterodimer with receptor activity-modifying protein 2 (RAMP2), and serves as the adrenomedullin (AM) receptor to control neovascularization, while CRLR and RAMP1 form the calcitonin gene-related peptide (CGRP) receptor. Here, we report the crystal structures of the RAMP2 extracellular domain alone and in the complex with the CRLR extracellular domain. The CRLR-RAMP2 complex exhibits several intermolecular interactions that were not observed in the previously reported CRLR-RAMP1 complex, and thus the shape of the putative ligand-binding pocket of CRLR-RAMP2 is distinct from that of CRLR-RAMP1. The CRLR-RAMP2 interactions were confirmed for the full-length proteins on the cell surface by site-specific photo-crosslinking. Mutagenesis revealed that AM binding requires RAMP2 residues that are not conserved in RAMP1. Therefore, the differences in both the shapes and the key residues of the binding pocket are essential for the ligand specificity.

PubMed: 22102369
DOI: 10.1002/pro.2003

Experimental method

X-RAY DIFFRACTION (2 Å)