Reconstructing the transport cycle in the sugar porter superfamily using coevolution-powered machine learning.

ABSTRACT: 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 h

SUBMITTER: Mitrovic D 

PROVIDER: S-EPMC10322152 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature