Abstract
ABC transporters are essential for cellular physiology. Humans have 48 ABC genes organized into seven distinct families. Of these genes, 44 (in five distinct families) encode for membrane transporters, of which several are involved in drug resistance and disease pathways resulting from transporter dysfunction. Over the last decade, advances in structural biology have vastly expanded our mechanistic understanding of human ABC transporter function, revealing details of their molecular arrangement, regulation, and interactions, facilitated in large part by advances in cryo-EM that have rendered hitherto inaccessible targets amenable to high-resolution structural analysis. As a result, experimentally determined structures of multiple members of each of the five families of ABC transporters in humans are now available. Here we review this recent progress, highlighting the physiological relevance of human ABC transporters and mechanistic insights gleaned from their direct structure determination. We also discuss the impact and limitations of model systems and structure prediction methods in understanding human ABC transporters and discuss current challenges and future research directions.
Original language | English (US) |
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Pages (from-to) | 275-300 |
Number of pages | 26 |
Journal | Annual Review of Biophysics |
Volume | 52 |
DOIs | |
State | Published - May 9 2023 |
Bibliographical note
Publisher Copyright:Copyright © 2023 by the author(s).
Keywords
- ATP-binding cassette transporter
- cryo-EM
- drug extrusion
- human disease
- lipid homeostasis
- membrane protein
PubMed: MeSH publication types
- Journal Article
- Review