6g6s
From Proteopedia
Crystal structure of human Acinus RNA recognition motif domain
Structural highlights
Function[ACINU_HUMAN] Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells.[1] [2] [3] [4] [5] Publication Abstract from PubMedAcinus is an abundant nuclear protein involved in apoptosis and splicing. It has been implicated in inducing apoptotic chromatin condensation and DNA fragmentation during programmed cell death. Acinus undergoes activation by proteolytic cleavage that produces a truncated p17 form that comprises only the RNA recognition motif (RRM) domain. We have determined the crystal structure of the human Acinus RRM domain (AcRRM) at 1.65 A resolution. It shows a classical four-stranded antiparallel beta-sheet fold with two flanking alpha-helices and an additional, non-classical alpha-helix at the C-terminus, which harbors the caspase-3 target sequence that is cleaved during Acinus activation. In the structure, the C-terminal alpha-helix partially occludes the potential ligand binding surface of the beta-sheet and hypothetically shields it from non-sequence specific interactions with RNA. Based on the comparison with other RRM-RNA complex structures, it is likely that the C-terminal alpha-helix changes its conformation with respect to the RRM core in order to enable RNA binding by Acinus. Crystal structure of human Acinus RNA recognition motif domain.,Fernandes H, Czapinska H, Grudziaz K, Bujnicki JM, Nowacka M PeerJ. 2018 Jul 4;6:e5163. doi: 10.7717/peerj.5163. eCollection 2018. PMID:30042883[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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