6c9m
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The Human NatA (Naa10/Naa15) amino-terminal acetyltransferase complex== |
| + | <StructureSection load='6c9m' size='340' side='right' caption='[[6c9m]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6c9m]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C9M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C9M FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[69c5|69c5]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/N-terminal_amino-acid_N(alpha)-acetyltransferase_NatA N-terminal amino-acid N(alpha)-acetyltransferase NatA], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.255 2.3.1.255] </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=6c9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6c9m OCA], [http://pdbe.org/6c9m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6c9m RCSB], [http://www.ebi.ac.uk/pdbsum/6c9m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6c9m ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/NAA10_HUMAN NAA10_HUMAN]] Premature aging appearance-developmental delay-cardiac arrhythmia syndrome;Microphthalmia, Lenz type. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/NAA15_HUMAN NAA15_HUMAN]] Auxillary subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity. The NAT activity may be important for vascular, hematopoietic and neuronal growth and development. Required to control retinal neovascularization in adult ocular endothelial cells. In complex with XRCC6 and XRCC5 (Ku80), up-regulates transcription from the osteocalcin promoter.<ref>PMID:11687548</ref> <ref>PMID:12145306</ref> <ref>PMID:15496142</ref> [[http://www.uniprot.org/uniprot/NAA10_HUMAN NAA10_HUMAN]] Catalytic subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity (PubMed:15496142, PubMed:19826488, PubMed:19420222, PubMed:20145209, PubMed:27708256, PubMed:25489052). Acetylates amino termini that are devoid of initiator methionine (PubMed:19420222). The alpha (N-terminal) acetyltransferase activity may be important for vascular, hematopoietic and neuronal growth and development. Without NAA15, displays epsilon (internal) acetyltransferase activity towards HIF1A, thereby promoting its degradation (PubMed:12464182). Represses MYLK kinase activity by acetylation, and thus represses tumor cell migration (PubMed:19826488). Acetylates, and stabilizes TSC2, thereby repressing mTOR activity and suppressing cancer development (PubMed:20145209). Acetylates HSPA1A and HSPA1B at 'Lys-77' which enhances its chaperone activity and leads to preferential binding to co-chaperone HOPX (PubMed:27708256). Acts as a negative regulator of sister chromatid cohesion during mitosis (PubMed:27422821).<ref>PMID:12464182</ref> <ref>PMID:15496142</ref> <ref>PMID:19420222</ref> <ref>PMID:19826488</ref> <ref>PMID:20145209</ref> <ref>PMID:25489052</ref> <ref>PMID:27422821</ref> <ref>PMID:27708256</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Co-translational N-terminal protein acetylation regulates many protein functions including degradation, folding, interprotein interactions, and targeting. Human NatA (hNatA), one of six conserved metazoan N-terminal acetyltransferases, contains Naa10 catalytic and Naa15 auxiliary subunits, and associates with the intrinsically disordered Huntingtin yeast two-hybrid protein K (HYPK). We report on the crystal structures of hNatA and hNatA/HYPK, and associated biochemical and enzymatic analyses. We demonstrate that hNatA contains unique features: a stabilizing inositol hexaphosphate (IP6) molecule and a metazoan-specific Naa15 domain that mediates high-affinity HYPK binding. We find that HYPK harbors intrinsic hNatA-specific inhibitory activity through a bipartite structure: a ubiquitin-associated domain that binds a hNaa15 metazoan-specific region and an N-terminal loop-helix region that distorts the hNaa10 active site. We show that HYPK binding blocks hNaa50 targeting to hNatA, likely limiting Naa50 ribosome localization in vivo. These studies provide a model for metazoan NAT activity and HYPK regulation of N-terminal acetylation. | ||
| - | + | Structure of Human NatA and Its Regulation by the Huntingtin Interacting Protein HYPK.,Gottlieb L, Marmorstein R Structure. 2018 Apr 23. pii: S0969-2126(18)30128-X. doi:, 10.1016/j.str.2018.04.003. PMID:29754825<ref>PMID:29754825</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 6c9m" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Gottlieb, L]] | [[Category: Gottlieb, L]] | ||
[[Category: Marmorstein, R]] | [[Category: Marmorstein, R]] | ||
| + | [[Category: N-terminal acetylation]] | ||
| + | [[Category: Nata]] | ||
| + | [[Category: Protein complex]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 05:55, 6 June 2018
The Human NatA (Naa10/Naa15) amino-terminal acetyltransferase complex
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