6nas

From Proteopedia

(Difference between revisions)

Revision as of 07:09, 16 March 2022

Ternary Complex of Ac-Alpha-Actin with Profilin and AcCoA-NAA80

Structural highlights

6nas is a 3 chain structure with sequence from Human and Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , ,
NonStd Res:	,
Gene:	NAA80, FUS2, NAT6 (HUMAN), PFN1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PROF1_HUMAN] Defects in PFN1 are the cause of amyotrophic lateral sclerosis 18 (ALS18) [MIM:614808]. A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.^[1]

Function

[ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [PROF1_HUMAN] Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.^[2] [NAA80_HUMAN] N-alpha-acetyltransferase that specifically mediates the acetylation of the acidic amino terminus of processed forms of beta- and gamma-actin (ACTB and ACTG, respectively) (PubMed:30028079, PubMed:29581253). N-terminal acetylation of processed beta- and gamma-actin regulates actin filament depolymerization and elongation (PubMed:29581253). In vivo, preferentially displays N-terminal acetyltransferase activity towards acid N-terminal sequences starting with Asp-Asp-Asp and Glu-Glu-Glu (PubMed:30028079, PubMed:29581253). In vitro, shows high activity towards Met-Asp-Glu-Leu and Met-Asp-Asp-Asp (PubMed:10644992, PubMed:29581307). May act as a tumor suppressor (PubMed:10644992).^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

About 80% of human proteins are amino-terminally acetylated (Nt-acetylated) by one of seven Nt-acetyltransferases (NATs). Actin, the most abundant protein in the cytoplasm, has its own dedicated NAT, NAA80, which acts posttranslationally and affects cytoskeleton assembly and cell motility. Here, we show that NAA80 does not associate with filamentous actin in cells, and its natural substrate is the monomeric actin-profilin complex, consistent with Nt-acetylation preceding polymerization. NAA80 Nt-acetylates actin-profilin much more efficiently than actin alone, suggesting that profilin acts as a chaperone for actin Nt-acetylation. We determined crystal structures of the NAA80-actin-profilin ternary complex, representing different actin isoforms and different states of the catalytic reaction and revealing the first structure of NAT-substrate complex at atomic resolution. The structural, biochemical, and cellular analysis of mutants shows how NAA80 has evolved to specifically recognize actin among all cellular proteins while targeting all six actin isoforms, which differ the most at the amino terminus.

Mechanism of actin N-terminal acetylation.,Rebowski G, Boczkowska M, Drazic A, Ree R, Goris M, Arnesen T, Dominguez R Sci Adv. 2020 Apr 8;6(15):eaay8793. doi: 10.1126/sciadv.aay8793. eCollection 2020, Apr. PMID:32284999^[7]

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

References

↑ Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH Jr, Landers JE. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012 Aug 23;488(7412):499-503. doi: 10.1038/nature11280. PMID:22801503 doi:10.1038/nature11280
↑ Shao J, Welch WJ, Diprospero NA, Diamond MI. Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. Mol Cell Biol. 2008 Sep;28(17):5196-208. doi: 10.1128/MCB.00079-08. Epub 2008 Jun, 23. PMID:18573880 doi:10.1128/MCB.00079-08
↑ Zegerman P, Bannister AJ, Kouzarides T. The putative tumour suppressor Fus-2 is an N-acetyltransferase. Oncogene. 2000 Jan 6;19(1):161-3. doi: 10.1038/sj.onc.1203234. PMID:10644992 doi:http://dx.doi.org/10.1038/sj.onc.1203234
↑ Drazic A, Aksnes H, Marie M, Boczkowska M, Varland S, Timmerman E, Foyn H, Glomnes N, Rebowski G, Impens F, Gevaert K, Dominguez R, Arnesen T. NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility. Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4399-4404. doi:, 10.1073/pnas.1718336115. Epub 2018 Mar 26. PMID:29581253 doi:http://dx.doi.org/10.1073/pnas.1718336115
↑ Goris M, Magin RS, Foyn H, Myklebust LM, Varland S, Ree R, Drazic A, Bhambra P, Stove SI, Baumann M, Haug BE, Marmorstein R, Arnesen T. Structural determinants and cellular environment define processed actin as the sole substrate of the N-terminal acetyltransferase NAA80. Proc Natl Acad Sci U S A. 2018 Mar 26. pii: 1719251115. doi:, 10.1073/pnas.1719251115. PMID:29581307 doi:http://dx.doi.org/10.1073/pnas.1719251115
↑ Wiame E, Tahay G, Tyteca D, Vertommen D, Stroobant V, Bommer GT, Van Schaftingen E. NAT6 acetylates the N-terminus of different forms of actin. FEBS J. 2018 Sep;285(17):3299-3316. doi: 10.1111/febs.14605. Epub 2018 Aug 13. PMID:30028079 doi:http://dx.doi.org/10.1111/febs.14605
↑ Rebowski G, Boczkowska M, Drazic A, Ree R, Goris M, Arnesen T, Dominguez R. Mechanism of actin N-terminal acetylation. Sci Adv. 2020 Apr 8;6(15):eaay8793. doi: 10.1126/sciadv.aay8793. eCollection 2020, Apr. PMID:32284999 doi:http://dx.doi.org/10.1126/sciadv.aay8793

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='6nas' size='340' side='right'caption='[[6nas]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6nas]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NAS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NAS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6nas]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NAS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NAS 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=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LAB:LATRUNCULIN+B'>LAB</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HIC:4-METHYL-HISTIDINE'>HIC</scene>, <scene name='pdbligand=KKD:'>KKD</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAA80, FUS2, NAT6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PFN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAA80, FUS2, NAT6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PFN1 ([https://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'>[http://proteopedia.org/fgij/fg.htm?mol=6nas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nas OCA], [http://pdbe.org/6nas PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nas RCSB], [http://www.ebi.ac.uk/pdbsum/6nas PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nas ProSAT]</span></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=6nas FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nas OCA], [https://pdbe.org/6nas PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nas RCSB], [https://www.ebi.ac.uk/pdbsum/6nas PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nas ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/PROF1_HUMAN PROF1_HUMAN]] Defects in PFN1 are the cause of amyotrophic lateral sclerosis 18 (ALS18) [MIM:[http://omim.org/entry/614808 614808]]. A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:22801503</ref>
+[[https://www.uniprot.org/uniprot/PROF1_HUMAN PROF1_HUMAN]] Defects in PFN1 are the cause of amyotrophic lateral sclerosis 18 (ALS18) [MIM:[https://omim.org/entry/614808 614808]]. A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:22801503</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/ACTS_RABIT ACTS_RABIT]] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [[http://www.uniprot.org/uniprot/PROF1_HUMAN PROF1_HUMAN]] Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.<ref>PMID:18573880</ref>  [[http://www.uniprot.org/uniprot/NAA80_HUMAN NAA80_HUMAN]] N-alpha-acetyltransferase that specifically mediates the acetylation of the acidic amino terminus of processed forms of beta- and gamma-actin (ACTB and ACTG, respectively) (PubMed:30028079, PubMed:29581253). N-terminal acetylation of processed beta- and gamma-actin regulates actin filament depolymerization and elongation (PubMed:29581253). In vivo, preferentially displays N-terminal acetyltransferase activity towards acid N-terminal sequences starting with Asp-Asp-Asp and Glu-Glu-Glu (PubMed:30028079, PubMed:29581253). In vitro, shows high activity towards Met-Asp-Glu-Leu and Met-Asp-Asp-Asp (PubMed:10644992, PubMed:29581307). May act as a tumor suppressor (PubMed:10644992).<ref>PMID:10644992</ref> <ref>PMID:29581253</ref> <ref>PMID:29581307</ref> <ref>PMID:30028079</ref>
+[[https://www.uniprot.org/uniprot/ACTS_RABIT ACTS_RABIT]] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [[https://www.uniprot.org/uniprot/PROF1_HUMAN PROF1_HUMAN]] Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.<ref>PMID:18573880</ref>  [[https://www.uniprot.org/uniprot/NAA80_HUMAN NAA80_HUMAN]] N-alpha-acetyltransferase that specifically mediates the acetylation of the acidic amino terminus of processed forms of beta- and gamma-actin (ACTB and ACTG, respectively) (PubMed:30028079, PubMed:29581253). N-terminal acetylation of processed beta- and gamma-actin regulates actin filament depolymerization and elongation (PubMed:29581253). In vivo, preferentially displays N-terminal acetyltransferase activity towards acid N-terminal sequences starting with Asp-Asp-Asp and Glu-Glu-Glu (PubMed:30028079, PubMed:29581253). In vitro, shows high activity towards Met-Asp-Glu-Leu and Met-Asp-Asp-Asp (PubMed:10644992, PubMed:29581307). May act as a tumor suppressor (PubMed:10644992).<ref>PMID:10644992</ref> <ref>PMID:29581253</ref> <ref>PMID:29581307</ref> <ref>PMID:30028079</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 ==See Also==
 *[[Actin 3D structures|Actin 3D structures]]
+*[[Profilin 3D Structures|Profilin 3D Structures]]
 == References ==
 <references/>

6nas

From Proteopedia

Revision as of 07:09, 16 March 2022

Ternary Complex of Ac-Alpha-Actin with Profilin and AcCoA-NAA80

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

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