TGF-beta is the founding member of a large family of biological molecules important in regulating cellular growth and differentiation, both in embryos as well as adults. Now, using x-ray diffraction at SSRL Beam Line 11-1 for macromolecular crystallography, Groppe, Hinck, and colleagues from the University of Texas Health Science Center at San Antonio have determined the structure of TGF-beta in complex with two of its cellular receptors, a finding that could lead to new insight as to how it functions as a suppressor of cell growth and as a stimulator of cell differentiation, processes which go awry in diseases such as cancer. The results are published in the February 1 edition of Molecular Cell.

TGF-beta is known to bind simultaneously to two receptors on the outside of cells called Type I and Type II receptors, and a complex of all three is required for the TGF-beta to perform its biological function. The recent study reveals that to form this complex, TGF-beta first binds to the Type II receptor, and the two molecules then cooperate to bind and recruit the Type I receptor through a composite interface.

The study also shows that TGF-beta and its receptors are nearly identical to others within the same protein family, namely the bone morphogenetic proteins (BMP) and the BMP receptors, yet in spite of their physical similarities, the two receptor complexes form in ways that are entirely distinct. Because BMPs are evolutionarily much more ancient, this difference provides insight into the evolution of organisms on the molecular level.

Jay Groppe, Cynthia S. Hinck, Payman Samavarchi-Tehrani, Chloe Zubieta, Jonathan P. Schuermann, Alex B. Taylor, Patricia M. Schwarz, Jeffrey L. Wrana, and Andrew P. Hinck (2008). "Cooperative assembly of TGF-b superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding" Mol. Cell 29(2): 157-168.

To learn more about this research see the full scientific highlight at:
http://www- ssrl.slac.stanford.edu/research/highlights_archive/tgfb.html