Structure and Mechanism of Human ABC Transporters

Amer Alam, Kaspar P. Locher

Research output: Contribution to journalReview articlepeer-review

54 Scopus citations

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 languageEnglish (US)
Pages (from-to)275-300
Number of pages26
JournalAnnual Review of Biophysics
Volume52
DOIs
StatePublished - 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

Fingerprint

Dive into the research topics of 'Structure and Mechanism of Human ABC Transporters'. Together they form a unique fingerprint.

Cite this