Structural basis for allosteric regulation of human phosphofructokinase-1
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F24%3A00597906" target="_blank" >RIV/61388955:_____/24:00597906 - isvavai.cz</a>
Result on the web
<a href="https://hdl.handle.net/11104/0355678" target="_blank" >https://hdl.handle.net/11104/0355678</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-024-51808-6" target="_blank" >10.1038/s41467-024-51808-6</a>
Alternative languages
Result language
angličtina
Original language name
Structural basis for allosteric regulation of human phosphofructokinase-1
Original language description
Phosphofructokinase-1 (PFK1) catalyzes the rate-limiting step of glycolysis, committing glucose to conversion into cellular energy. PFK1 is highly regulated to respond to the changing energy needs of the cell. In bacteria, the structural basis of PFK1 regulation is a textbook example of allostery, molecular signals of low and high cellular energy promote transition between an active R-state and inactive T-state conformation, respectively. Little is known, however, about the structural basis for regulation of eukaryotic PFK1. Here, we determine structures of the human liver isoform of PFK1 (PFKL) in the R- and T-state by cryoEM, providing insight into eukaryotic PFK1 allosteric regulatory mechanisms. The T-state structure reveals conformational differences between the bacterial and eukaryotic enzyme, the mechanisms of allosteric inhibition by ATP binding at multiple sites, and an autoinhibitory role of the C-terminus in stabilizing the T-state. We also determine structures of PFKL filaments that define the mechanism of higher-order assembly and demonstrate that these structures are necessary for higher-order assembly of PFKL in cells.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
<a href="/en/project/GA23-06437S" target="_blank" >GA23-06437S: Allostery and spatial organization in glycolysis: the role of phosphofructokinase 1</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications
ISSN
2041-1723
e-ISSN
2041-1723
Volume of the periodical
15
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
7323
UT code for WoS article
001298087400004
EID of the result in the Scopus database
2-s2.0-85201935759