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6g2h

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Revision as of 07:50, 6 November 2019

Filament of acetyl-CoA carboxylase and BRCT domains of BRCA1 (ACC-BRCT) core at 4.6 A resolution

Structural highlights

6g2h is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	ACACA, ACAC, ACC1, ACCA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ACACA_HUMAN] Defects in ACACA are a cause of acetyl-CoA carboxylase 1 deficiency (ACACAD) [MIM:613933]; also known as ACAC deficiency or ACC deficiency. An inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth.^[1]

Function

[ACACA_HUMAN] Catalyzes the rate-limiting reaction in the biogenesis of long-chain fatty acids. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.^[2]

Publication Abstract from PubMed

Acetyl-CoA carboxylase catalyses the ATP-dependent carboxylation of acetyl-CoA, a rate-limiting step in fatty acid biosynthesis(1,2). Eukaryotic acetyl-CoA carboxylases are large, homodimeric multienzymes. Human acetyl-CoA carboxylase occurs in two isoforms: the metabolic, cytosolic ACC1, and ACC2, which is anchored to the outer mitochondrial membrane and controls fatty acid beta-oxidation(1,3). ACC1 is regulated by a complex interplay of phosphorylation, binding of allosteric regulators and protein-protein interactions, which is further linked to filament formation(1,4-8). These filaments were discovered in vitro and in vivo 50 years ago(7,9,10), but the structural basis of ACC1 polymerization and regulation remains unknown. Here, we identify distinct activated and inhibited ACC1 filament forms. We obtained cryo-electron microscopy structures of an activated filament that is allosterically induced by citrate (ACC-citrate), and an inactivated filament form that results from binding of the BRCT domains of the breast cancer type 1 susceptibility protein (BRCA1). While non-polymeric ACC1 is highly dynamic, filament formation locks ACC1 into different catalytically competent or incompetent conformational states. This unique mechanism of enzyme regulation via large-scale conformational changes observed in ACC1 has potential uses in engineering of switchable biosynthetic systems. Dissecting the regulation of acetyl-CoA carboxylase opens new paths towards counteracting upregulation of fatty acid biosynthesis in disease.

Structural basis for regulation of human acetyl-CoA carboxylase.,Hunkeler M, Hagmann A, Stuttfeld E, Chami M, Guri Y, Stahlberg H, Maier T Nature. 2018 Jun 13. pii: 10.1038/s41586-018-0201-4. doi:, 10.1038/s41586-018-0201-4. PMID:29899443^[3]

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

References

↑ Blom W, de Muinck Keizer SM, Scholte HR. Acetyl-CoA carboxylase deficiency: an inborn error of de novo fatty acid synthesis. N Engl J Med. 1981 Aug 20;305(8):465-6. PMID:6114432 doi:http://dx.doi.org/10.1056/NEJM198108203050820
↑ Colbert CL, Kim CW, Moon YA, Henry L, Palnitkar M, McKean WB, Fitzgerald K, Deisenhofer J, Horton JD, Kwon HJ. Crystal structure of Spot 14, a modulator of fatty acid synthesis. Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18820-5. Epub 2010 Oct 15. PMID:20952656 doi:10.1073/pnas.1012736107
↑ Hunkeler M, Hagmann A, Stuttfeld E, Chami M, Guri Y, Stahlberg H, Maier T. Structural basis for regulation of human acetyl-CoA carboxylase. Nature. 2018 Jun 13. pii: 10.1038/s41586-018-0201-4. doi:, 10.1038/s41586-018-0201-4. PMID:29899443 doi:http://dx.doi.org/10.1038/s41586-018-0201-4

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6g2h"

@@ Line 1: / Line 1: @@
-{{Large structure}}
 ==Filament of acetyl-CoA carboxylase and BRCT domains of BRCA1 (ACC-BRCT) core at 4.6 A resolution==
-<StructureSection load='6g2h' size='340' side='right' caption='[[6g2h]], [[Resolution|resolution]] 4.60&Aring;' scene=''>
+<StructureSection load='6g2h' size='340' side='right'caption='[[6g2h]], [[Resolution|resolution]] 4.60&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6g2h]] is a 6 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=6G2H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G2H FirstGlance]. <br>
@@ Line 7: / Line 7: @@
 <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=6g2h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g2h OCA], [http://pdbe.org/6g2h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g2h RCSB], [http://www.ebi.ac.uk/pdbsum/6g2h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g2h ProSAT]</span></td></tr>
 </table>
-{{Large structure}}
 == Disease ==
 [[http://www.uniprot.org/uniprot/ACACA_HUMAN ACACA_HUMAN]] Defects in ACACA are a cause of acetyl-CoA carboxylase 1 deficiency (ACACAD) [MIM:[http://omim.org/entry/613933 613933]]; also known as ACAC deficiency or ACC deficiency. An inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth.<ref>PMID:6114432</ref>
@@ Line 26: / Line 25: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Chami, M]]
 [[Category: Hagmann, A]]

6g2h

From Proteopedia

Revision as of 07:50, 6 November 2019

Filament of acetyl-CoA carboxylase and BRCT domains of BRCA1 (ACC-BRCT) core at 4.6 A resolution

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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