Structural biology of betaglycan and endoglin, membrane-bound co-receptors of the TGF-beta family
Abstract
Betaglycan and endoglin, membrane-bound co-receptors of the TGF-β family, are required to mediate the signaling of a select subset of TGF-β family ligands, TGF-β2 and InhA, and BMP-9 and BMP-10, respectively. Previous biochemical and biophysical methods suggested alternative modes of ligand binding might be responsible for these co-receptors to selectively recognize and potentiate the functions of their ligands, yet the molecular details were lacking. Recent progress determining structures of betaglycan and endoglin, both alone and as bound to their cognate ligands, is presented herein. The structures reveal relatively minor, but very significant structural differences that lead to entirely different modes of ligand binding. The different modes of binding nonetheless share certain commonalities, such as multivalency, which imparts the co-receptors with very high affinity for their cognate ligands, but at the same time provides a mechanism for release by stepwise binding of the signaling receptors, both of which are essential for their functions.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 10, 2019
- Source ID
- 10.1177/1535370219881160
Entities
People
- Andrew P Hinck
- Morkos A. Henen
- Sun Kyung Kim
Organizations
- American Heart Association
- Cancer Prevention and Research Institute of Texas
- Mansoura University
- National Institutes of Health
- Robert A. Welch Foundation
- United States Army Medical Command
- University of California, San Francisco
- University of Pittsburgh