1EDY

CRYSTAL STRUCTURE OF RAT ALPHA 1-MACROGLOBULIN RECEPTOR BINDING DOMAIN

Summary for 1EDY

• Entry DOI: 10.2210/pdb1edy/pdb
• Descriptor: ALPHA 1-MACROGLOBULIN (2 entities in total)
• Functional Keywords: beta sandwich, pseudo-symmetric dimer, protein binding
• Biological source: Rattus norvegicus (Norway rat)
• Total number of polymer chains: 2
• Total formula weight: 30762.83

Authors

Xiao, T.,DeCamp, D.L.,Sprang, S.R. (deposition date: 2000-01-28, release date: 2000-12-01, Last modification date: 2024-02-07)

Primary citation

Xiao, T.,DeCamp, D.L.,Spran, S.R.
Structure of a rat alpha 1-macroglobulin receptor-binding domain dimer.
Protein Sci., 9:1889-1897, 2000

PubMed Abstract: Alpha-macroglobulin inhibits a broad spectrum of proteinases by forming macromolecular cages inside which proteinases are cross-linked and trapped. Upon formation of a complex with proteinase, alpha-macroglobulin undergoes a large conformational change that results in the exposure of its receptor-binding domain (RBD). Engagement of this domain by alpha-macroglobulin receptor permits clearance of the alpha-macroglobulin: proteinase complex from circulation. The crystal structure of rat alpha1-macroglobulin RBD has been determined at 2.3 A resolution. The RBD is composed of a nine-stranded beta-sandwich and a single alpha-helix that has been implicated as part of the receptor binding site and that lies on the surface of the beta-sandwich. The crystallographic asymmetric unit contains a dimer of RBDs related by approximate twofold symmetry such that the putative receptor recognition sites of the two monomers are contiguous. By gel filtration and ultracentrifugation, it is shown that RBD dimers form in solution with a dissociation constant of approximately 50 microM. The structure of the RBD dimer might mimic a conformation of transformed alpha-macroglobulin in which the proposed receptor binding residues are exposed on one face of the dimer. A pair of phenylalanine residues replaces a cystine that is conserved in other members of the macroglobulin family. These residues participate in a network of aromatic side-chain interactions that appears to stabilize the dimer interface.

PubMed: 11106161

Experimental method

X-RAY DIFFRACTION (2.3 Å)