The role of salt bridge networks in the stability of the yeast hexose transporter 1.
Glucose receptors
Glucose transporters
Hxt1
Rgt2
Salt bridge-forming residues
Yeast
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
received:
31
08
2023
revised:
06
10
2023
accepted:
12
10
2023
medline:
6
11
2023
pubmed:
17
10
2023
entrez:
16
10
2023
Statut:
ppublish
Résumé
The yeast S. cerevisiae preferably metabolizes glucose through aerobic glycolysis. Glucose transport is facilitated by multiple hexose transporters (Hxts), and their expression and activity are tightly regulated by multiple mechanisms. However, detailed structural and functional analyses of Hxts remain limited, largely due to the lack of crystal structure. Homology modeling was used to build a 3D structural model for the yeast glucose transporter Hxt1 and investigate the effects of site directed mutations on Hxt1 stability and glucose transport activity. The conserved salt bridge-forming residues observed in the human Glut4 and the yeast glucose receptor Rgt2 were identified within and between the two 6-transmembrane spanning segments of Hxt1. Most of the RGT2 mutations that disrupt the salt bridge networks were known to cause constitutive signal generation, whereas the corresponding substitutions in HXT1 were shown to decrease Hxt1 stability. While substitutions of the two residues in the salt bridge 2 in Glut4-E329Q and E393D-were reported to abolish glucose transport, the equivalent substitutions in Hxt1 (D382Q and E454D) did not affect Hxt1 glucose transport activity. Substitutions of equivalent salt bridge-forming residues in Hxt1, Rgt2, and Glut4 are predicted to lock them in an inward-facing conformation but lead to different functional consequences. The salt bridge networks in yeast and human glucose transporters and yeast glucose receptors may play different roles in maintaining their structural and functional integrity.
Sections du résumé
BACKGROUND
The yeast S. cerevisiae preferably metabolizes glucose through aerobic glycolysis. Glucose transport is facilitated by multiple hexose transporters (Hxts), and their expression and activity are tightly regulated by multiple mechanisms. However, detailed structural and functional analyses of Hxts remain limited, largely due to the lack of crystal structure.
METHODS
Homology modeling was used to build a 3D structural model for the yeast glucose transporter Hxt1 and investigate the effects of site directed mutations on Hxt1 stability and glucose transport activity.
RESULTS
The conserved salt bridge-forming residues observed in the human Glut4 and the yeast glucose receptor Rgt2 were identified within and between the two 6-transmembrane spanning segments of Hxt1. Most of the RGT2 mutations that disrupt the salt bridge networks were known to cause constitutive signal generation, whereas the corresponding substitutions in HXT1 were shown to decrease Hxt1 stability. While substitutions of the two residues in the salt bridge 2 in Glut4-E329Q and E393D-were reported to abolish glucose transport, the equivalent substitutions in Hxt1 (D382Q and E454D) did not affect Hxt1 glucose transport activity.
CONCLUSIONS
Substitutions of equivalent salt bridge-forming residues in Hxt1, Rgt2, and Glut4 are predicted to lock them in an inward-facing conformation but lead to different functional consequences.
GENERAL SIGNIFICANCE
The salt bridge networks in yeast and human glucose transporters and yeast glucose receptors may play different roles in maintaining their structural and functional integrity.
Identifiants
pubmed: 37844739
pii: S0304-4165(23)00188-5
doi: 10.1016/j.bbagen.2023.130490
pii:
doi:
Substances chimiques
Monosaccharide Transport Proteins
0
Saccharomyces cerevisiae Proteins
0
Glucose Transport Proteins, Facilitative
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
130490Informations de copyright
Copyright © 2023. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare there are no competing interests to disclose.