Authors:	Ford, Robert C. Hellmich, Ute A.
Title:	What monomeric nucleotide binding domains can teach us about dimeric ABC proteins
Online publication date:	29-Jun-2021
Year of first publication:	2020
Language:	english
Abstract:	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.
DDC:	540 Chemie 540 Chemistry and allied sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 09 Chemie, Pharmazie u. Geowissensch.
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-6132
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY-NC-ND
Information on rights of use:	https://creativecommons.org/licenses/by-nc-nd/4.0/
Journal:	FEBS letters 594 23
Pages or article number:	3857 3875
Publisher:	Wiley
Publisher place:	Chichester
Issue date:	2020
ISSN:	1873-3468
Publisher URL:	https://doi.org/10.1002/1873-3468.13921
Publisher DOI:	10.1002/1873-3468.13921
Appears in collections:	JGU-Publikationen