Selecting for Altered Substrate Specificity Reveals the Evolutionary Flexibility of ATP-Binding Cassette Transporters.
ABC transporter
Saccharomyces cerevisiae
Yarrowia lipolytica
autocrine selection
fungal mating
pheromone transporter
protein evolution
random mutagenesis
substrate selectivity
Journal
Current biology : CB
ISSN: 1879-0445
Titre abrégé: Curr Biol
Pays: England
ID NLM: 9107782
Informations de publication
Date de publication:
04 05 2020
04 05 2020
Historique:
received:
10
10
2019
revised:
20
01
2020
accepted:
24
02
2020
pubmed:
30
3
2020
medline:
19
8
2021
entrez:
30
3
2020
Statut:
ppublish
Résumé
ATP-binding cassette (ABC) transporters are the largest family of ATP-hydrolyzing transporters, which import or export substrates across membranes, and have members in every sequenced genome. Structural studies and biochemistry highlight the contrast between the global structural similarity of homologous transporters and the enormous diversity of their substrates. How do ABC transporters evolve to carry such diverse molecules and what variations in their amino acid sequence alter their substrate selectivity? We mutagenized the transmembrane domains of a conserved fungal ABC transporter that exports a mating pheromone and selected for mutants that export a non-cognate pheromone. Mutations that alter export selectivity cover a region that is larger than expected for a localized substrate-binding site. Individual selected clones have multiple mutations, which have broadly additive contributions to specific transport activity. Our results suggest that multiple positions influence substrate selectivity, leading to alternative evolutionary paths toward selectivity for particular substrates and explaining the number and diversity of ABC transporters.
Identifiants
pubmed: 32220325
pii: S0960-9822(20)30284-0
doi: 10.1016/j.cub.2020.02.077
pmc: PMC7243462
mid: NIHMS1572001
pii:
doi:
Substances chimiques
ATP-Binding Cassette Transporters
0
Fungal Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1689-1702.e6Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM043987
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM120996
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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