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6n3f

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Revision as of 11:17, 18 December 2019

Structure of HIV Tat-specific factor 1 U2AF Homology Motif bound to SF3b1 ULM5

Structural highlights

6n3f is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	HTATSF1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HTSF1_HUMAN] Functions as a general transcription factor playing a role in the process of transcriptional elongation. May mediate the reciprocal stimulatory effect of splicing on transcriptional elongation. In case of infection by HIV-1, it is up-regulated by the HIV-1 proteins NEF and gp120, acts as a cofactor required for the Tat-enhanced transcription of the virus.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8]

Publication Abstract from PubMed

The transcription elongation and pre-mRNA splicing factor Tat-SF1 associates with the U2 small nuclear ribonucleoprotein (snRNP) of the spliceosome. However, the direct binding partner and underlying interactions mediating the Tat-SF1-U2 snRNP association remain unknown. Here, we identified SF3b1 as a Tat-SF1-interacting subunit of the U2 snRNP. Our 1.1 A resolution crystal structure revealed that Tat-SF1 contains a U2AF homology motif (UHM) protein-protein interaction module. We demonstrated that Tat-SF1 preferentially and directly binds the SF3b1 subunit compared to other U2AF ligand motif (ULM)-containing splicing factors, and further established that SF3b1 association depends on the integrity of the Tat-SF1 UHM. We next compared the Tat-SF1 binding affinities for each of the five known SF3b1 ULMs and then determined the structures of representative high- and low-affinity SF3b1 ULM complexes with the Tat-SF1 UHM at 1.9 A and 2.1 A resolutions, respectively. These structures revealed a canonical UHM-ULM interface, comprising a Tat-SF1 binding pocket for a ULM tryptophan (SF3b1 W338) and electrostatic interactions with a basic ULM tail. Importantly, we found that SF3b1 regulates Tat-SF1 levels and that these two factors influence expression of overlapping representative transcripts, consistent with a functional partnership of Tat-SF1 and SF3b1. Altogether, these results define a new molecular interface of the Tat-SF1-U2 snRNP complex for gene regulation.

The pre-mRNA splicing and transcription factor Tat-SF1 is a functional partner of the spliceosome SF3b1 subunit via a U2AF homology motif interface.,Loerch S, Leach JR, Horner SW, Maji D, Jenkins JL, Pulvino M, Kielkopf CL J Biol Chem. 2018 Dec 19. pii: RA118.006764. doi: 10.1074/jbc.RA118.006764. PMID:30567737^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Parada CA, Roeder RG. A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription. EMBO J. 1999 Jul 1;18(13):3688-701. PMID:10393184 doi:10.1093/emboj/18.13.3688
↑ Kim JB, Yamaguchi Y, Wada T, Handa H, Sharp PA. Tat-SF1 protein associates with RAP30 and human SPT5 proteins. Mol Cell Biol. 1999 Sep;19(9):5960-8. PMID:10454543
↑ Fong YW, Zhou Q. Relief of two built-In autoinhibitory mechanisms in P-TEFb is required for assembly of a multicomponent transcription elongation complex at the human immunodeficiency virus type 1 promoter. Mol Cell Biol. 2000 Aug;20(16):5897-907. PMID:10913173
↑ Simmons A, Aluvihare V, McMichael A. Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators. Immunity. 2001 Jun;14(6):763-77. PMID:11420046
↑ Fong YW, Zhou Q. Stimulatory effect of splicing factors on transcriptional elongation. Nature. 2001 Dec 20-27;414(6866):929-33. PMID:11780068 doi:http://dx.doi.org/10.1038/414929a
↑ Misse D, Gajardo J, Oblet C, Religa A, Riquet N, Mathieu D, Yssel H, Veas F. Soluble HIV-1 gp120 enhances HIV-1 replication in non-dividing CD4+ T cells, mediated via cell signaling and Tat cofactor overexpression. AIDS. 2005 Jun 10;19(9):897-905. PMID:15905670
↑ Zhou Q, Sharp PA. Tat-SF1: cofactor for stimulation of transcriptional elongation by HIV-1 Tat. Science. 1996 Oct 25;274(5287):605-10. PMID:8849451
↑ Li XY, Green MR. The HIV-1 Tat cellular coactivator Tat-SF1 is a general transcription elongation factor. Genes Dev. 1998 Oct 1;12(19):2992-6. PMID:9765201
↑ Loerch S, Leach JR, Horner SW, Maji D, Jenkins JL, Pulvino M, Kielkopf CL. The pre-mRNA splicing and transcription factor Tat-SF1 is a functional partner of the spliceosome SF3b1 subunit via a U2AF homology motif interface. J Biol Chem. 2018 Dec 19. pii: RA118.006764. doi: 10.1074/jbc.RA118.006764. PMID:30567737 doi:http://dx.doi.org/10.1074/jbc.RA118.006764

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6n3f"

@@ Line 1: / Line 1: @@
 ==Structure of HIV Tat-specific factor 1 U2AF Homology Motif bound to SF3b1 ULM5==
-<StructureSection load='6n3f' size='340' side='right'  caption='[[6n3f]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='6n3f' size='340' side='right'caption='[[6n3f]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6n3f]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N3F FirstGlance]. <br>
@@ Line 24: / Line 24: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Jenkins, J L]]
 [[Category: Kielkopf, C L]]

6n3f

From Proteopedia

Revision as of 11:17, 18 December 2019

Structure of HIV Tat-specific factor 1 U2AF Homology Motif bound to SF3b1 ULM5

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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