Crystal structure of a phosphorylated Smad2: Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-β signaling Journal Article

  

Authors:	Wu, J. W.; Hu, M.; Chai, J. J.; Seoane, J.; Huse, M.; Li, C.; Rigotti, D. J.; Kyin, S.; Muir, T. W.; Fairman, R.; Massague, J.; Shi, Y. G.
Article Title:	Crystal structure of a phosphorylated Smad2: Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-β signaling
Abstract:	Ligand-induced phosphorylation of the receptor-regulated Smads (R-Smads) is essential in the receptor Ser/Thr kinase-mediated TGF-beta signaling. The crystal structure of a phosphorylated Smad2, at 1.8 Angstrom resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. The pSer binding surface on the MH2 domain, frequently targeted for inactivation in cancers, is highly conserved among the Co- and R-Smads. This finding, together with mutagenesis data, pinpoints a functional interface between Smad2 and Smad4. In addition, the pSer binding surface on the MH2 domain coincides with the surface on R-Smads that is required for docking interactions with the serine-phosphorylated receptor kinases. These observations define a bifunctional role for the MH2 domain as a pSer-X-pSer binding module in receptor Ser/Thr kinase signaling pathways.
Keywords:	gene; protein; receptor; specificity; activation; complex; tyrosine kinases; src; 3-dimensional structure; ser(465)
Journal Title:	Molecular Cell
Volume:	8
Issue:	6
ISSN:	1097-2765
Publisher:	Cell Press
Date Published:	2001-12-01
Start Page:	1277
End Page:	1289
Language:	English
ACCESSION:	WOS:000172907800015
DOI:	10.1016/s1097-2765(01)00421-x
PROVIDER:	wos
PUBMED:	11779503
Notes:	Article -- Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/75887