What monomeric nucleotide binding domains can teach us about dimeric ABC proteins
Robert C Ford1, Ute A Hellmich2,3
1Faculty of Biology Medicine and Health, The University of Manchester, UK.
FEBS Letters
|September 4, 2020
Summary
ATP binding cassette (ABC) transporter function relies on nucleotide binding domains (NBDs) dimerizing. This study explores why NBD dimerization is often missing in isolated NBDs and full-length ABC transporters.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- ATP binding cassette (ABC) transporters utilize ATP-dependent conformational changes for substrate transport across membranes.
- Nucleotide binding domains (NBDs) are crucial for ABC transporter function, with ATP binding typically inducing NBD dimerization.
Purpose of the Study:
- To investigate the factors influencing nucleotide binding domain (NBD) dimerization in ATP binding cassette (ABC) transporters.
- To address the discrepancy between expected and observed NBD dimerization in both isolated NBDs and full-length ABC proteins.
Main Methods:
- Comparative analysis of NBD dimerization in isolated domains versus full-length transporters.
- Review of structural and functional data concerning NBD-nucleotide interactions.
- Exploration of the roles of transmembrane domains (TMDs) and linkers in NBD association.
Main Results:
- Isolated NBDs often fail to dimerize despite nucleotide binding capability.
- NBD-dimerized, outward-facing states are less frequent than anticipated even in complete ABC transporters.
- The precise drivers of NBD interaction and the influence of TMDs/linkers remain areas requiring further investigation.
Conclusions:
- NBD dimerization is a complex process not solely dependent on nucleotide binding.
- Transmembrane domains and linker regions likely play significant roles in modulating NBD association and ABC transporter function.
- Further research is needed to fully elucidate the mechanisms governing NBD dimerization and its impact on ABC transporter activity.
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