What monomeric nucleotide binding domains can teach us about dimeric ABC proteins

FEBS Letters

article

Robert C. Ford¹  Ute A. Hellmich² 

[1] Faculty of Biology Medicine and Health, The University of Manchester;Department of Chemistry, Johannes Gutenberg-University;Centre for Biomolecular Magnetic Resonance (BMRZ), Goethe-University

关键词: ATP binding cassette;    dimerization;    domain interactions;    domain linkers;    membrane transporter;    nucleotide binding domain;    protein structure and function;   

DOI  :  10.1002/1873-3468.13921

来源: John Wiley & Sons Ltd.

【 摘 要 】

The classic conceptualization of ATP binding cassette (ABC) transporter function is an ATP-dependent conformational change coupled to transport of a substrate across a biological membrane via the transmembrane domains (TMDs). The binding of two ATP molecules within the transporter’s two nucleotide binding domains (NBDs) induces their dimerization. Despite retaining the ability to bind nucleotides, isolated NBDs frequently fail to dimerize. ABC proteins without a TMD, for example ABCE and ABCF, have NBDs tethered via elaborate linkers, further supporting that NBD dimerization does not readily occur for isolated NBDs. Intriguingly, even in full-length transporters, the NBD-dimerized, outward-facing state is not as frequently observed as might be expected. This leads to questions regarding what drives NBD interaction and the role of the TMDs or linkers. Understanding the NBD–nucleotide interaction and the subsequent NBD dimerization is thus pivotal for understanding ABC transporter activity in general. Here, we hope to provide new insights into ABC protein function by discussing the perplexing issue of (missing) NBD dimerization in isolation and in the context of full-length ABC proteins.

【 授权许可】

Unknown