Format

Send to

Choose Destination
Mol Endocrinol. 2010 Jul;24(7):1469-77. doi: 10.1210/me.2009-0496. Epub 2010 May 19.

Bone morphogenetic protein-2 and -6 heterodimer illustrates the nature of ligand-receptor assembly.

Author information

1
Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Abstract

TGF-beta superfamily ligands are homo- or heterodimeric and recruit two type I and two type II Ser/Thr kinase receptors to initiate a transmembrane signaling cascade. Even with the known structure of the homodimer ligands in complex with extracellular domains of both receptor types, the sequential assembly of the signaling complex with its cognate receptors in the cell membrane remains elusive. We generated a bone morphogenetic protein-2/-6 heterodimer carrying two asymmetric interfaces for each receptor type. We demonstrate that the heterodimer possesses high affinity to both receptor types and increased Smad1-dependent signaling activity by both cell-based and chondrogenesis assays. Furthermore, we find that the minimal signaling complex consists of two type II receptors and one type I receptor per dimer. Our study reveals how the engineered heterodimers may use their independent binding interfaces to differentially recruit the different receptors for each receptor type to create new biological properties.

PMID:
20484413
PMCID:
PMC2903903
DOI:
10.1210/me.2009-0496
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center