6hip | pdb_00006hip
Structure of SPF45 UHM bound to HIV-1 Rev ULM
Structural highlights
Function[SPF45_HUMAN] Splice factor that binds to the single stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia.[1] Publication Abstract from PubMedThe HIV-1 protein Rev is essential for virus replication and ensures the expression of partially spliced and unspliced transcripts. We identified a ULM (UHM ligand motif) motif in the Arginine-Rich Motif (ARM) of the Rev protein. ULMs (UHM ligand motif) mediate protein interactions during spliceosome assembly by binding to UHM (U2AF homology motifs) domains. Using NMR, biophysical methods and crystallography we show that the Rev ULM binds to the UHMs of U2AF65 and SPF45. The highly conserved Trp45 in the Rev ULM is crucial for UHM binding in vitro, for Rev co-precipitation with U2AF65 in human cells and for proper processing of HIV transcripts. Thus, Rev-ULM interactions with UHM splicing factors contribute to the regulation of HIV-1 transcript processing, also at the splicing level. The Rev ULM is an example of viral mimicry of host short linear motifs that enables the virus to interfere with the host molecular machinery. Modulation of HIV-1 gene expression by binding of a ULM motif in the Rev protein to UHM-containing splicing factors.,Pabis M, Corsini L, Vincendeau M, Tripsianes K, Gibson TJ, Brack-Werner R, Sattler M Nucleic Acids Res. 2019 May 21;47(9):4859-4871. doi: 10.1093/nar/gkz185. PMID:30892606[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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