6nbw

From Proteopedia

(Difference between revisions)

Current revision

Ternary Complex of Beta/Gamma-Actin with Profilin and AnCoA-NAA80

Structural highlights

6nbw is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.5Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ACTB_HUMAN Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:607371. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.^[1] Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:243310. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.^[2]

Function

ACTB_HUMAN Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

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^[3]

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

References

↑ Procaccio V, Salazar G, Ono S, Styers ML, Gearing M, Davila A, Jimenez R, Juncos J, Gutekunst CA, Meroni G, Fontanella B, Sontag E, Sontag JM, Faundez V, Wainer BH. A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia. Am J Hum Genet. 2006 Jun;78(6):947-60. Epub 2006 Apr 21. PMID:16685646 doi:S0002-9297(07)63917-2
↑ Riviere JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat Genet. 2012 Feb 26;44(4):440-4, S1-2. doi: 10.1038/ng.1091. PMID:22366783 doi:10.1038/ng.1091
↑ 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/6nbw"

Categories: Homo sapiens | Large Structures | Boczkowska M | Dominguez R | Rebowski G

@@ Line 3: / Line 3: @@
 <StructureSection load='6nbw' size='340' side='right'caption='[[6nbw]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6nbw]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NBW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6nbw]] is a 3 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=6NBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NBW FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=SOP:[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL+(3R)-3-HYDROXY-2,2-DIMETHYL-4-OXO-4-{[3-OXO-3-({2-[(2-OXOPROPYL)THIO]ETHYL}AMINO)PROPYL]AMINO}BUTYL+DIHYDROGEN+DIPHOSPHATE'>SOP</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</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></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=HIC:4-METHYL-HISTIDINE'>HIC</scene>, <scene name='pdbligand=LAB:LATRUNCULIN+B'>LAB</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SOP:[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]METHYL+(3R)-3-HYDROXY-2,2-DIMETHYL-4-OXO-4-{[3-OXO-3-({2-[(2-OXOPROPYL)THIO]ETHYL}AMINO)PROPYL]AMINO}BUTYL+DIHYDROGEN+DIPHOSPHATE'>SOP</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6nbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nbw OCA], [https://pdbe.org/6nbw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nbw RCSB], [https://www.ebi.ac.uk/pdbsum/6nbw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nbw ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN]] Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:[https://omim.org/entry/607371 607371]]. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.<ref>PMID:16685646</ref>   Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:[https://omim.org/entry/243310 243310]]. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.<ref>PMID:22366783</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>
+[https://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN] Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:[https://omim.org/entry/607371 607371]. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.<ref>PMID:16685646</ref>   Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:[https://omim.org/entry/243310 243310]. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.<ref>PMID:22366783</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN]] 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>
+[https://www.uniprot.org/uniprot/ACTB_HUMAN ACTB_HUMAN] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 31: / Line 30: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Boczkowska, M]]
+[[Category: Boczkowska M]]
-[[Category: Dominguez, R]]
+[[Category: Dominguez R]]
-[[Category: Rebowski, G]]
+[[Category: Rebowski G]]
-[[Category: Acetylation]]
-[[Category: Cytosolic protein]]
-[[Category: Naa80]]
-[[Category: Structural protein-transferase complex]]

6nbw

From Proteopedia

Current revision

Ternary Complex of Beta/Gamma-Actin with Profilin and AnCoA-NAA80

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

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