6ano | pdb_00006ano
Crystal structure of human FLASH N-terminal domain
Structural highlights
FunctionC8AP2_HUMAN Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation. Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis. Required for histone gene transcription and progression through S phase.[1] [2] [3] [4] Publication Abstract from PubMedUnlike canonical pre-mRNAs, animal replication-dependent histone pre-mRNAs lack introns and are processed at the 3'-end by a mechanism distinct from cleavage and polyadenylation. They have a 3' stem loop and histone downstream element (HDE) that are recognized by stem-loop binding protein (SLBP) and U7 snRNP, respectively. The N-terminal domain (NTD) of Lsm11, a component of U7 snRNP, interacts with FLASH NTD and these two proteins recruit the histone cleavage complex containing the CPSF-73 endonuclease for the cleavage reaction. Here, we determined crystal structures of FLASH NTD and found that it forms a coiled-coil dimer. Using solution light scattering, we characterized the stoichiometry of the FLASH NTD-Lsm11 NTD complex and found that it is a 2:1 heterotrimer, which is supported by observations from analytical ultracentrifugation and crosslinking. The N-terminal domains of FLASH and Lsm11 form a 2:1 heterotrimer for histone pre-mRNA 3'-end processing.,Aik WS, Lin MH, Tan D, Tripathy A, Marzluff WF, Dominski Z, Chou CY, Tong L PLoS One. 2017 Oct 11;12(10):e0186034. doi: 10.1371/journal.pone.0186034., eCollection 2017. PMID:29020104[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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