Targeted degradation of ABC transporters in health and disease.

Abstract:

:ATP binding cassette (ABC) transporters comprise an extended protein family involved in the transport of a broad spectrum of solutes across membranes. They consist of a common architecture including two ATP-binding domains converting chemical energy into conformational changes and two transmembrane domains facilitating transport via alternating access. This review focuses on the biogenesis, and more precisely, on the degradation of mammalian ABC transporters in the endoplasmic reticulum (ER). We enlighten the ER-associated degradation pathway in the context of misfolded, misassembled or tightly regulated ABC transporters with a closer view on the cystic fibrosis transmembrane conductance regulator (CFTR) and the transporter associated with antigen processing (TAP), which plays an essential role in the adaptive immunity. Three rather different scenarios affecting the stability and degradation of ABC transporters are discussed: (1) misfolded domains caused by a lack of proper intra- and intermolecular contacts within the ABC transporters, (2) deficient assembly with auxiliary factors, and (3) arrest and accumulation of an intermediate or 'dead-end' state in the transport cycle, which is prone to be recognized by the ER-associated degradation machinery.

journal_name

J Bioenerg Biomembr

authors

Nikles D,Tampé R

doi

10.1007/s10863-007-9120-z

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

489-97

issue

5-6

eissn

0145-479X

issn

1573-6881

journal_volume

39

pub_type

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