SCANNING-DELETION ANALYSIS OF THE EXTRACELLULAR DOMAIN OF THE TGF-BETA RECEPTOR-TYPE-II

There are three main types of receptors for TGF-beta termed receptor t ype I, type II and type III. TGF-beta receptor type II has a crucial r ole in the cell's responsiveness to TGF-beta as it is mandatory for TG F-beta binding to the signaling complex (receptor type I and type II). Here we have used a scanning-deletion mutagenesis approach to determi ne the core binding domain of the extracellular domain of receptor typ e II that is required for interaction with TGF-beta. Deletions of thre e amino acids were systematically introduced at intervals of five amin o acids in order to scan the N- and C-terminus of the extracellular do main of the receptor. We find that the N-terminal region which is devo id of cysteine residues is not critical for ligand binding. Similarly, the C-terminal region, i.e., the amino acids flanking the transmembra ne domain, are dispensable for binding. These results suggest that the central 100 amino acid span that is rich in cysteine residues is the core binding domain for TGF-beta. (C) 1996 Academic Press, Inc.