Sökning: WFRF:(Alleva E) >
Reconstructing the ...
Reconstructing the transport cycle in the sugar porter superfamily using coevolution-powered machine learning
-
- Mitrovic, Darko (författare)
- KTH,Biofysik,Science for Life Laboratory, SciLifeLab
-
- McComas, Sarah E. (författare)
- Stockholms universitet,KTH,Science for Life Laboratory, SciLifeLab,Biofysik,Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),KTH Royal Institute of Technology, Sweden
-
- Alleva, Claudia (författare)
- Stockholms universitet,KTH,Science for Life Laboratory, SciLifeLab,Biofysik,Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),KTH Royal Institute of Technology, Sweden
-
visa fler...
-
- Bonaccorsi, Marta (författare)
- Stockholms universitet,KTH,Biofysik,Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),KTH Royal Institute of Technology, Sweden
-
- Drew, David (författare)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden
-
- Delemotte, Lucie (författare)
- KTH,Biofysik,Science for Life Laboratory, SciLifeLab
-
visa färre...
-
(creator_code:org_t)
- eLife Sciences Publications, Ltd, 2023
- 2023
- Engelska.
-
Ingår i: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 12
- Relaterad länk:
-
https://doi.org/10.7...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.7...
-
https://urn.kb.se/re...
-
visa färre...
Abstract
Ämnesord
Stäng
- Sugar porters (SPs) represent the largest group of secondary-active transporters. Some members, such as the glucose transporters (GLUTs), are well known for their role in maintaining blood glucose homeostasis in mammals, with their expression upregulated in many types of cancers. Because only a few sugar porter structures have been determined, mechanistic models have been constructed by piecing together structural states of distantly related proteins. Current GLUT transport models are predominantly descriptive and oversimplified. Here, we have combined coevolution analysis and comparative modeling, to predict structures of the entire sugar porter superfamily in each state of the transport cycle. We have analyzed the state-specific contacts inferred from coevolving residue pairs and shown how this information can be used to rapidly generate free-energy landscapes consistent with experimental estimates, as illustrated here for the mammalian fructose transporter GLUT5. By comparing many different sugar porter models and scrutinizing their sequence, we have been able to define the molecular determinants of the transport cycle, which are conserved throughout the sugar porter superfamily. We have also been able to highlight differences leading to the emergence of proton-coupling, validating, and extending the previously proposed latch mechanism. Our computational approach is transferable to any transporter, and to other protein families in general.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
Nyckelord
- membrane protein
- molecular biophysics
- molecular dynamics simulations
- molecular modeling
- none
- structural biology
- structure prediction
- transporter
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
-
eLIFE
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas