The Arabidopsis AtSWEET13 transporter discriminates sugars by selective facial and positional substrate recognition

Transporters are targeted by endogenous metabolites and exogenous molecules to reach cellular destinations, but it is generally not understood how different substrate classes exploit the same transporter’s mechanism. Any disclosure of plasticity in transporter mechanism when treated with different substrates becomes critical for developing general selectivity principles in membrane transport catalysis. Using extensive molecular dynamics simulations with an enhanced sampling approach, we select the Arabidopsis sugar transporter AtSWEET13 as a model system to identify the basis for glucose versus sucrose molecular recognition and transport. Here we find that AtSWEET13 chemical selectivity originates from a conserved substrate facial selectivity demonstrated when committing alternate access, despite mono-/di-saccharides experiencing differing degrees of conformational and positional freedom throughout other stages of transport. However, substrate interactions with structural hallmarks associated with known functional annotations can help reinforce selective preferences in molecular transport.

Methods
Molecular dynamics trajectories were generated using AMBER18, performed on NCSA Blue Waters supercomputing resources. Analyses were performed with python scripts.

This work has been performed by Austin T. Weigle & Diwakar Shukla at the University of Illinois Urbana-Champaign.

This Dryad dataset has been made available in compliance with the "minimum dataset"/source data requirement per the Data Availability guidelines by Communications Biology.

For further inquiries concerning further data availability, please contact Prof. Diwakar Shukla at [e-mail]. Austin T. Weigle (https://orcid.org/0000-0002-1619-2452) prepared this Dryad repository.