PMID- 10615055 OWN - NLM STAT- MEDLINE DCOM- 20000120 LR - 20220227 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 287 IP - 5450 DP - 2000 Jan 7 TI - Structural basis of Smad2 recognition by the Smad anchor for receptor activation. PG - 92-7 AB - The Smad proteins mediate transforming growth factor-beta (TGFbeta) signaling from the transmembrane serine-threonine receptor kinases to the nucleus. The Smad anchor for receptor activation (SARA) recruits Smad2 to the TGFbeta receptors for phosphorylation. The crystal structure of a Smad2 MH2 domain in complex with the Smad-binding domain (SBD) of SARA has been determined at 2.2 angstrom resolution. SARA SBD, in an extended conformation comprising a rigid coil, an alpha helix, and a beta strand, interacts with the beta sheet and the three-helix bundle of Smad2. Recognition between the SARA rigid coil and the Smad2 beta sheet is essential for specificity, whereas interactions between the SARA beta strand and the Smad2 three-helix bundle contribute significantly to binding affinity. Comparison of the structures between Smad2 and a comediator Smad suggests a model for how receptor-regulated Smads are recognized by the type I receptors. FAU - Wu, G AU - Wu G AD - Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Princeton, NJ 08544, USA. FAU - Chen, Y G AU - Chen YG FAU - Ozdamar, B AU - Ozdamar B FAU - Gyuricza, C A AU - Gyuricza CA FAU - Chong, P A AU - Chong PA FAU - Wrana, J L AU - Wrana JL FAU - Massague, J AU - Massague J FAU - Shi, Y AU - Shi Y LA - eng SI - PDB/1DEV GR - CA85171/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Carrier Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Receptors, Transforming Growth Factor beta) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Smad2 Protein) RN - 0 (Trans-Activators) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.30 (Activin Receptors, Type I) RN - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I) SB - IM MH - *Activin Receptors, Type I MH - Amino Acid Sequence MH - Binding Sites MH - Carrier Proteins/*chemistry/*metabolism MH - Crystallography, X-Ray MH - DNA-Binding Proteins/*chemistry/genetics/*metabolism MH - Hydrogen Bonding MH - Models, Molecular MH - Molecular Sequence Data MH - Mutation MH - Phosphorylation MH - Point Mutation MH - Protein Conformation MH - Protein Serine-Threonine Kinases/chemistry/genetics/metabolism MH - Protein Structure, Secondary MH - Protein Structure, Tertiary MH - Receptor, Transforming Growth Factor-beta Type I MH - Receptors, Transforming Growth Factor beta/chemistry/genetics/metabolism MH - Recombinant Fusion Proteins/chemistry/metabolism MH - Signal Transduction MH - Smad2 Protein MH - Trans-Activators/*chemistry/genetics/*metabolism MH - Zinc Fingers EDAT- 1999/12/30 00:00 MHDA- 1999/12/30 00:01 CRDT- 1999/12/30 00:00 PHST- 1999/12/30 00:00 [pubmed] PHST- 1999/12/30 00:01 [medline] PHST- 1999/12/30 00:00 [entrez] AID - 8162 [pii] AID - 10.1126/science.287.5450.92 [doi] PST - ppublish SO - Science. 2000 Jan 7;287(5450):92-7. doi: 10.1126/science.287.5450.92.