Asset Details
Do you wish to reserve the book?
Structural basis for regulation of human acetyl-CoA carboxylase
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Structural basis for regulation of human acetyl-CoA carboxylase
Do you wish to request the book?
Structural basis for regulation of human acetyl-CoA carboxylase
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Structural basis for regulation of human acetyl-CoA carboxylase
2018
Overview
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 β-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.
Cryo-electron microscopy studies of distinct, catalytically active and inactive filaments of human acetyl-CoA carboxylase 1 reveal the structural basis of its regulation.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 82/16
/ 82/29
/ 82/58
/ 82/80
/ 82/83
/ Acetyl-CoA Carboxylase - chemistry
/ Acetyl-CoA Carboxylase - metabolism
/ Acetyl-CoA Carboxylase - ultrastructure
/ Animals
/ BRCA1 Protein - pharmacology
/ Cancer
/ Enzymes
/ Humanities and Social Sciences
/ Humans
/ Isoforms
/ Kinases
/ Letter
/ Ligases
/ Lipids
/ Polymerization - drug effects
/ Protein Domains - drug effects
/ Protein Structure, Quaternary - drug effects
/ Protein-protein interactions
/ Proteins
/ Science
