TCB Publications - Abstract
Tanmay S. Chavan, Ricky C. Cheng, Tao Jiang, Irimpan I. Mathews, Richard A. Stein, Antoine Koehl, Hassane S. Mchaourab, Emad Tajkhorshid, and Merritt Maduke. A CLC-ec1 mutant reveals global conformational change and suggests a unifying mechanism for the Cl-/H+ transport cycle. eLife, 9:e53479, 2020. (PMC: PMC7253180)
for H
). Transport-cycle models to
describe and explain this unusual mechanism have been proposed based on
known CLC structures. While the proposed models harmonize many
experimental findings, there have remained gaps and inconsistencies in our
understanding. One limitation has been that global conformational change -
which occurs in all conventional transporter mechanisms - has not been
observed in any high-resolution structure. Here, we describe the 2.6 Å
structure of a CLC mutant designed to mimic the fully H-loaded
transporter. This structure reveals a global conformational change to a state
that has improved accessibility for the Cl substrate from the extracellular
side and new conformations for two key glutamate residues. Based on this
new structure, together with DEER measurements, MD simulations, and
functional studies, we propose a unified model of the CLC transport
mechanism that reconciles existing data on all CLC-type proteins.
