title: Crystal structure of unphosphorylated STAT3 core fragment.
abstract: Signal transducers and activators of transcription (STATs) are latent cytoplasmic transcriptional factors that play an important role in cytokine and growth factor signaling. Here we report a 3.05 A-resolution crystal structure of an unphosphorylated STAT3 core fragment. The overall monomeric structure is very similar to that of the phosphorylated STAT3 core fragment. However, the dimer interface observed in the unphosphorylated STAT1 core fragment structure is absent in the STAT3 structure. Solution studies further demonstrate that the core fragment of STAT3 is primarily monomeric. Mutations corresponding to those in STAT1, which lead to disruption of the core fragment interface and prolonged tyrosine phosphorylation, show little or no effect on the tyrosine phosphorylation kinetics of STAT3. These results highlight the structural and biochemical differences between STAT3 and STAT1, and suggest different regulation mechanisms of these two proteins.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1000, Houston, TX 77030, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Ren
authors.forename: Xiang
authors.initials: X
authors.lastname: Mao
authors.forename: Claudia
authors.initials: C
authors.lastname: Mertens
authors.forename: Ravi
authors.initials: R
authors.lastname: Krishnaraj
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.forename: Pijus K
authors.initials: PK
authors.lastname: Mandal
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Romanowski
authors.forename: John S
authors.initials: JS
authors.lastname: McMurray
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D003461:Crystallography; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D050794:STAT1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse