Apr 4, 2020

Role of transmembrane helix 6 in substrate recognition of the amino acid transporter MhsT

BioRxiv : the Preprint Server for Biology
Poul NissenI. O. Schwarz


MhsT of Bacillus halodurans is a transporter of hydrophobic amino acids and a homologue of the eukaryotic SLC6 family of Na+-dependent symporters for amino acids, neurotransmitters, osmolytes, or creatine. The broad range of transported amino acids by MhsT prompted the investigation of the substrate recognition mechanism. Here, we report six new substrate-bound structures of MhsT, which, in conjunction with functional studies, reveal how the flexibility of a Gly-Met-Gly (GMG) motif in the unwound region of transmembrane segment 6 (TM6) is central for the recognition of substrates of different size by tailoring the binding site shape and volume. MhsT mutants, harboring substitutions within the unwound GMG loop and substrate binding pocket that mimick the binding sites of eukaryotic SLC6A18/B0AT3 and SLC6A19/B0AT1 transporters of neutral amino acids, exhibited impaired transport of aromatic amino acids that require a large binding site volume. Conservation of a general (G/A/C){Phi}G motif among eukaryotic members of SLC6 family suggests a role for this loop in a common mechanism for substrate recognition and translocation by SLC6 transporters of broad substrate specificity.

  • References
  • Citations


  • We're still populating references for this paper, please check back later.
  • References
  • Citations


  • This paper may not have been cited yet.

Mentioned in this Paper

Anatomy, Regional

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

Journal of Psychiatric and Mental Health Nursing
Matthew CallenderValentina Lugli
Proceedings of the National Academy of Sciences of the United States of America
M. QuickJ. A. Javitch
© 2020 Meta ULC. All rights reserved