skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: High resolution structures of the bone morphogenetic protein type II receptor in two crystal forms: Implications for ligand binding

Abstract

BMPRII is a type II TGF-{beta} serine threonine kinase receptor which is integral to the bone morphogenetic protein (BMP) signalling pathway. It is known to bind BMP and growth differentiation factor (GDF) ligands, and has overlapping ligand specificity with the activin type II receptor, ActRII. In contrast to activin and TGF-{beta} type ligands, BMPs bind to type II receptors with lower affinity than type I receptors. Crystals of the BMPRII ectodomain were grown in two different forms, both of which diffracted to high resolution. The tetragonal form exhibited some disorder, whereas the entire polypeptide was seen in the orthorhombic form. The two structures retain the basic three-finger toxin fold of other TGF-{beta} receptor ectodomains, and share the main hydrophobic patch used by ActRII to bind various ligands. However, they present different conformations of the A-loop at the periphery of the proposed ligand-binding interface, in conjunction with rearrangement of a disulfide bridge within the loop. This particular disulfide (Cys94-Cys117) is only present in BMPRII and activin receptors, suggesting that it is important for their likely shared mode of binding. Evidence is presented that the two crystal forms represent ligand-bound and free conformations of BMPRII. Comparison with the solved structure of ActRIImore » bound to BMP2 suggests that His87, unique amongst TGF-{beta} receptors, may play a key role in ligand recognition.« less

Authors:
 [1];  [1];  [2]
  1. Department of Biochemistry, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9001 (New Zealand)
  2. Department of Biochemistry, Otago School of Medical Sciences, University of Otago, P.O. Box 56, Dunedin 9001 (New Zealand). E-mail: sue.cutfield@otago.ac.nz
Publication Date:
OSTI Identifier:
20857934
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 351; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2006.10.109; PII: S0006-291X(06)02342-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AFFINITY; CRYSTALS; DISULFIDES; FINGERS; LIGANDS; ORTHORHOMBIC LATTICES; POLYPEPTIDES; RECEPTORS; SERINE; SKELETON; SPATIAL RESOLUTION; THREONINE; TOXINS

Citation Formats

Mace, Peter D., Cutfield, John F., and Cutfield, Sue M. High resolution structures of the bone morphogenetic protein type II receptor in two crystal forms: Implications for ligand binding. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.10.109.
Mace, Peter D., Cutfield, John F., & Cutfield, Sue M. High resolution structures of the bone morphogenetic protein type II receptor in two crystal forms: Implications for ligand binding. United States. doi:10.1016/j.bbrc.2006.10.109.
Mace, Peter D., Cutfield, John F., and Cutfield, Sue M. Fri . "High resolution structures of the bone morphogenetic protein type II receptor in two crystal forms: Implications for ligand binding". United States. doi:10.1016/j.bbrc.2006.10.109.
@article{osti_20857934,
title = {High resolution structures of the bone morphogenetic protein type II receptor in two crystal forms: Implications for ligand binding},
author = {Mace, Peter D. and Cutfield, John F. and Cutfield, Sue M.},
abstractNote = {BMPRII is a type II TGF-{beta} serine threonine kinase receptor which is integral to the bone morphogenetic protein (BMP) signalling pathway. It is known to bind BMP and growth differentiation factor (GDF) ligands, and has overlapping ligand specificity with the activin type II receptor, ActRII. In contrast to activin and TGF-{beta} type ligands, BMPs bind to type II receptors with lower affinity than type I receptors. Crystals of the BMPRII ectodomain were grown in two different forms, both of which diffracted to high resolution. The tetragonal form exhibited some disorder, whereas the entire polypeptide was seen in the orthorhombic form. The two structures retain the basic three-finger toxin fold of other TGF-{beta} receptor ectodomains, and share the main hydrophobic patch used by ActRII to bind various ligands. However, they present different conformations of the A-loop at the periphery of the proposed ligand-binding interface, in conjunction with rearrangement of a disulfide bridge within the loop. This particular disulfide (Cys94-Cys117) is only present in BMPRII and activin receptors, suggesting that it is important for their likely shared mode of binding. Evidence is presented that the two crystal forms represent ligand-bound and free conformations of BMPRII. Comparison with the solved structure of ActRII bound to BMP2 suggests that His87, unique amongst TGF-{beta} receptors, may play a key role in ligand recognition.},
doi = {10.1016/j.bbrc.2006.10.109},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 351,
place = {United States},
year = {Fri Dec 29 00:00:00 EST 2006},
month = {Fri Dec 29 00:00:00 EST 2006}
}