Distinct Substrate Transport Mechanism Identified in Homologous Sugar Transporters

Kevin J. Cheng, Balaji Selvam, Liqing Chen, Diwakar Shukla

Research output: Contribution to journalArticle

Abstract

SWEETs and their prokaryotic counterparts SemiSWEETs were recently classified as transporters that translocate sugar across cellular membranes. SemiSWEETs are commonly used as a model system to infer biological properties of SWEETs; however, this presumes that the homologues are comparable to begin with. We evaluate this presumption by comparing their protein dynamics and substrate transport mechanism using 532 μs of simulation data in conjunction with Markov state models (MSMs). MSM weighted conformational landscape plots reveal significant differences between SWEETs and SemiSWEETs despite having similar structural topology. The presence of glucose reduces the free energy barrier between the functionally important intermediate states to enhance the transport process, while the substrate has no effect on SemiSWEET. The glucose adopts more rotational degrees of freedom in SWEET, while its conformation is restricted for SemiSWEET. Our study provides biological insights on the unexplored novelty of difference in the functional mechanism of two close homologous proteins.

Original languageEnglish (US)
Pages (from-to)8411-8418
Number of pages8
JournalJournal of Physical Chemistry B
Volume123
Issue number40
DOIs
StatePublished - Oct 10 2019

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transporter
sugars
Sugars
glucose
Glucose
Substrates
proteins
Proteins
Energy barriers
data simulation
Free energy
Conformations
topology
degrees of freedom
plots
free energy
Topology
membranes
Membranes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Distinct Substrate Transport Mechanism Identified in Homologous Sugar Transporters. / Cheng, Kevin J.; Selvam, Balaji; Chen, Liqing; Shukla, Diwakar.

In: Journal of Physical Chemistry B, Vol. 123, No. 40, 10.10.2019, p. 8411-8418.

Research output: Contribution to journalArticle

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