Shah, Parantu K. ; Buslje, Cristina Marino ; Sowdhamini, R. (2001) Structural determinants of binding and specificity in transforming growth factor-receptor interactions Proteins: Structure, Function, and Bioinformatics, 45 (4). pp. 408-420. ISSN 0887-3585
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Official URL: http://onlinelibrary.wiley.com/doi/10.1002/prot.10...
Related URL: http://dx.doi.org/10.1002/prot.10010
Abstract
Transforming growth factor (TGF-β) protein families are cytokines that occur as a large number of homologous proteins. Three major subgroups of these proteins with marked specificities for their receptors have been found-TGF-β, activin/inhibin, and bone morphogenic protein. Although structural information is available for some members of the TGF-β family of ligands and receptors, very little is known about the way these growth factors interact with the extracellular domains of their cell surface receptors, especially the type II receptor. In addition, the elements that are the determinants of binding and specificity of the ligands are poorly understood. The structure of the extracellular domain of the receptor is a three-finger fold similar to some toxin structures. Amino acid exchanges between multiply aligned homologous sequences of type II receptors point to a residue at the surface, specifically finger 1, as the determinant of ligand specificity and complex formation. The "knuckle" epitope of ligands was predicted to be the surface that interacts with the type II receptor. The residues on strands β2, β3, β7, β8 and the loop region joining β2 and β3 and joining β7 and β8 of the ligands were identified as determinants of binding and specificity. These results are supported by studies on the docking of the type II receptor to the ligand dimer-type I receptor complex.
Item Type: | Article |
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Source: | Copyright of this article belongs to John Wiley and Sons. |
Keywords: | Protein-protein Interactions; Evolutionary Trace Analysis; Hydrophobic Interface; Charge Distribution; Sequence Analysis; Alignments |
ID Code: | 61239 |
Deposited On: | 15 Sep 2011 03:54 |
Last Modified: | 18 May 2016 11:01 |
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