5ctt

From Proteopedia

(Difference between revisions)

Revision as of 17:51, 12 July 2016

Crystal structure of human SART3/TIP110 NLS-mouse importin alpha complex

Structural highlights

5ctt is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	5ctq, 5ctr
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SART3_HUMAN] Defects in SART3 are the cause of disseminated superficial actinic porokeratosis type 1 (DSAP1) [MIM:175900]. DSAP1 is an autosomal dominant disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border, developing during the third or fourth decade of life on sun-exposed areas of skin.^[1]

Function

[IMA1_MOUSE] Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. [SART3_HUMAN] Regulates Tat transactivation activity through direct interaction. May be a cellular factor for HIV-1 gene expression and viral replication.^[2]

Publication Abstract from PubMed

Squamous cell carcinoma antigen recognized by T-cells 3 (SART3) is a U4/U6 recycling factor as well as a targeting factor of USP4 and USP15. However, the details of how SART3 recognizes these deubiquitinases and how they get subsequently translocated into the nucleus are not known. Here, we present the crystal structures of the SART3 half-a-tetratricopeptide (HAT) repeat domain alone and in complex with the domain present in ubiquitin-specific protease (DUSP)-ubiquitin-like (UBL) domains of ubiquitin specific protease 4 (USP4). The 12 HAT repeats of SART3 are in two sub-domains (HAT-N and HAT-C) forming a dimer through HAT-C. USP4 binds SART3 at the opposite surface of the HAT-C dimer interface utilizing the beta-structured linker between the DUSP and the UBL domains. The binding affinities of USP4 and USP15 to SART3 are 0.9 muM and 0.2 muM, respectively. The complex structure of SART3 nuclear localization signal (NLS) and importin-alpha reveals bipartite binding, and removal of SART3 NLS prevents the entry of USP4 (and USP15) into the nucleus and abrogates the subsequent deubiquitinase activity of USP4.

Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3.,Park JK, Das T, Song EJ, Kim EE Nucleic Acids Res. 2016 Apr 7. pii: gkw218. PMID:27060135^[3]

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

References

↑ Zhang ZH, Niu ZM, Yuan WT, Zhao JJ, Jiang FX, Zhang J, Chai B, Cui F, Chen W, Lian CH, Xiang LH, Xu SJ, Liu WD, Zheng ZZ, Huang W. A mutation in SART3 gene in a Chinese pedigree with disseminated superficial actinic porokeratosis. Br J Dermatol. 2005 Apr;152(4):658-63. PMID:15840095 doi:10.1111/j.1365-2133.2005.06443.x
↑ Liu Y, Li J, Kim BO, Pace BS, He JJ. HIV-1 Tat protein-mediated transactivation of the HIV-1 long terminal repeat promoter is potentiated by a novel nuclear Tat-interacting protein of 110 kDa, Tip110. J Biol Chem. 2002 Jun 28;277(26):23854-63. Epub 2002 Apr 16. PMID:11959860 doi:10.1074/jbc.M200773200
↑ Park JK, Das T, Song EJ, Kim EE. Structural basis for recruiting and shuttling of the spliceosomal deubiquitinase USP4 by SART3. Nucleic Acids Res. 2016 Apr 7. pii: gkw218. PMID:27060135 doi:http://dx.doi.org/10.1093/nar/gkw218

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ctt"

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[5ctt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CTT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CTT FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ctq|5ctq]], [[5ctr|5ctr]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ctt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ctt OCA], [http://pdbe.org/5ctt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ctt RCSB], [http://www.ebi.ac.uk/pdbsum/5ctt PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ctt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ctt OCA], [http://pdbe.org/5ctt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ctt RCSB], [http://www.ebi.ac.uk/pdbsum/5ctt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ctt ProSAT]</span></td></tr>
 </table>
 == Disease ==

5ctt

From Proteopedia

Revision as of 17:51, 12 July 2016

Crystal structure of human SART3/TIP110 NLS-mouse importin alpha complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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