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| | <SX load='6pw9' size='340' side='right' viewer='molstar' caption='[[6pw9]], [[Resolution|resolution]] 4.03Å' scene=''> | | <SX load='6pw9' size='340' side='right' viewer='molstar' caption='[[6pw9]], [[Resolution|resolution]] 4.03Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6pw9]] is a 4 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=6PW9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PW9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pw9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PW9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PW9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.03Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAA50, MAK3, NAT13, NAT5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NAA15, GA19, NARG1, NATH, TBDN100 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NAA10, ARD1, ARD1A, TE2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), HYPK, C15orf63, HSPC136 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6pw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pw9 OCA], [https://pdbe.org/6pw9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pw9 RCSB], [https://www.ebi.ac.uk/pdbsum/6pw9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pw9 ProSAT]</span></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://proteopedia.org/fgij/fg.htm?mol=6pw9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pw9 OCA], [http://pdbe.org/6pw9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pw9 RCSB], [http://www.ebi.ac.uk/pdbsum/6pw9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pw9 ProSAT]</span></td></tr> | + | |
| | </table> | | </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 == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HYPK_HUMAN HYPK_HUMAN]] Has a chaperone-like activity preventing polyglutamine (polyQ) aggregation of HTT. Protects against HTT polyQ-mediated apoptosis in Neuro2a neuronal cells. Required for optimal NAA10-NAA15 complex-mediated N-terminal acetylation.<ref>PMID:17947297</ref> <ref>PMID:20154145</ref> [[http://www.uniprot.org/uniprot/NAA50_HUMAN NAA50_HUMAN]] Probable catalytic component of the NAA11-NAA15 complex which displays alpha (N-terminal) acetyltransferase activity.<ref>PMID:16507339</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> [[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> | + | [https://www.uniprot.org/uniprot/NAA50_HUMAN NAA50_HUMAN] Probable catalytic component of the NAA11-NAA15 complex which displays alpha (N-terminal) acetyltransferase activity.<ref>PMID:16507339</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Deng, S]] | + | [[Category: Deng S]] |
| - | [[Category: Marmorstein, R]] | + | [[Category: Marmorstein R]] |
| - | [[Category: Hypk]]
| + | |
| - | [[Category: Naa50]]
| + | |
| - | [[Category: Nata]]
| + | |
| - | [[Category: Nate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
NAA50_HUMAN Probable catalytic component of the NAA11-NAA15 complex which displays alpha (N-terminal) acetyltransferase activity.[1]
Publication Abstract from PubMed
The human N-terminal acetyltransferase E (NatE) contains NAA10 and NAA50 catalytic, and NAA15 auxiliary subunits and associates with HYPK, a protein with intrinsic NAA10 inhibitory activity. NatE co-translationally acetylates the N-terminus of half the proteome to mediate diverse biological processes, including protein half-life, localization, and interaction. The molecular basis for how NatE and HYPK cooperate is unknown. Here, we report the cryo-EM structures of human NatE and NatE/HYPK complexes and associated biochemistry. We reveal that NAA50 and HYPK exhibit negative cooperative binding to NAA15 in vitro and in human cells by inducing NAA15 shifts in opposing directions. NAA50 and HYPK each contribute to NAA10 activity inhibition through structural alteration of the NAA10 substrate-binding site. NAA50 activity is increased through NAA15 tethering, but is inhibited by HYPK through structural alteration of the NatE substrate-binding site. These studies reveal the molecular basis for coordinated N-terminal acetylation by NatE and HYPK.
Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK.,Deng S, McTiernan N, Wei X, Arnesen T, Marmorstein R Nat Commun. 2020 Feb 10;11(1):818. doi: 10.1038/s41467-020-14584-7. PMID:32042062[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Arnesen T, Anderson D, Torsvik J, Halseth HB, Varhaug JE, Lillehaug JR. Cloning and characterization of hNAT5/hSAN: an evolutionarily conserved component of the NatA protein N-alpha-acetyltransferase complex. Gene. 2006 Apr 26;371(2):291-5. Epub 2006 Feb 28. PMID:16507339 doi:http://dx.doi.org/S0378-1119(05)00749-3
- ↑ Deng S, McTiernan N, Wei X, Arnesen T, Marmorstein R. Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK. Nat Commun. 2020 Feb 10;11(1):818. doi: 10.1038/s41467-020-14584-7. PMID:32042062 doi:http://dx.doi.org/10.1038/s41467-020-14584-7
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