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5h43

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Revision as of 07:23, 13 December 2017

Structural and mechanistical studies of the nuclear import by Importin-alpha

Structural highlights

5h43 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.
Gene:	KPNA2, RCH1, SRP1 (HUMAN), KAT8, MOF, MYST1 (HUMAN)
Activity:	Histone acetyltransferase, with EC number 2.3.1.48
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IMA1_HUMAN] 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. [KAT8_HUMAN] Histone acetyltransferase which may be involved in transcriptional activation. May influence the function of ATM. As part of the MSL complex it is involved in acetylation of nucleosomal histone H4 producing specifically H4K16ac. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. That activity is less specific than the one of the MSL complex.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The histone acetyltransferase MOF (males-absent-on-the-first) acetylates the histone H4, a modification important for many biological processes, including chromatin organization, transcriptional regulation, DNA replication, recombination and repair, as well as autophagy. Depletion of MOF induces serious consequences due to the reduction of histone acetylation, such as nuclear morphological defects and cancer. Despite the critical roles of MOF in the nucleus, the structural or functional mechanisms of the nucleocytoplasmic transport of MOF remain elusive. Here, we identified novel importin alpha1-specific nuclear localization signals (NLSs) in the N-terminal of human MOF. The crystal structure of MOF NLSs in complex with importin alpha1 further revealed a unique binding mode of MOF, with two independent NLSs binding to importin alpha1 major and minor sites, respectively. The second NLS of MOF displays an unexpected alpha-helical conformation in the C-terminus, with more extensive contacts with importin alpha1 not limited in the minor site. Mutations of the key residues on MOF and importin alpha1 lead to the reduction of their interaction as well as the nuclear import of MOF, revealing an essential role of NLS2 of MOF in interacting with importin alpha1 minor site. Taken together, we provide structural mechanisms underlying the nucleocytoplasmic transport of MOF, which will be of great importance in understanding the functional regulation of MOF in various biological processes.

Structural insights into the nuclear import of the histone acetyltransferase MOF by importin alpha1.,Zheng W, Wang R, Liu X, Tian S, Yao B, Chen A, Jin S, Li Y Traffic. 2017 Oct 9. doi: 10.1111/tra.12534. PMID:28991411^[4]

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

References

↑ Pardo PS, Leung JK, Lucchesi JC, Pereira-Smith OM. MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation. J Biol Chem. 2002 Dec 27;277(52):50860-6. Epub 2002 Oct 22. PMID:12397079 doi:10.1074/jbc.M203839200
↑ Gupta A, Sharma GG, Young CS, Agarwal M, Smith ER, Paull TT, Lucchesi JC, Khanna KK, Ludwig T, Pandita TK. Involvement of human MOF in ATM function. Mol Cell Biol. 2005 Jun;25(12):5292-305. PMID:15923642 doi:25/12/5292
↑ Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, Washburn MP, Conaway JW, Conaway RC. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J Biol Chem. 2010 Feb 12;285(7):4268-72. doi: 10.1074/jbc.C109.087981. Epub 2009 , Dec 14. PMID:20018852 doi:10.1074/jbc.C109.087981
↑ Zheng W, Wang R, Liu X, Tian S, Yao B, Chen A, Jin S, Li Y. Structural insights into the nuclear import of the histone acetyltransferase MOF by importin alpha1. Traffic. 2017 Oct 9. doi: 10.1111/tra.12534. PMID:28991411 doi:http://dx.doi.org/10.1111/tra.12534

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/5h43"

@@ Line 3: / Line 3: @@
 <StructureSection load='5h43' size='340' side='right' caption='[[5h43]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5h43]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H43 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H43 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5h43]] 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=5H43 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5H43 FirstGlance]. <br>
-</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KPNA2, RCH1, SRP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), KAT8, MOF, MYST1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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=5h43 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h43 OCA], [http://pdbe.org/5h43 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h43 RCSB], [http://www.ebi.ac.uk/pdbsum/5h43 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h43 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 </StructureSection>
 [[Category: Histone acetyltransferase]]
+[[Category: Human]]
 [[Category: Li, Y]]
 [[Category: Wang, R]]

5h43

From Proteopedia

Revision as of 07:23, 13 December 2017

Structural and mechanistical studies of the nuclear import by Importin-alpha

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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