A frozen portrait of a warm channel.

In order to understand protein function, the field of structural biology makes extensive use of cryogenic electron microscopy (cryo-EM), a technique that enables structure determination at atomic resolution following embedding of protein particles in vitreous ice. Considering the profound effects of temperature on macromolecule function, an important-but often neglected-question is how the frozen particles relate to the actual protein conformations at physiological temperatures. In a recent study, Hu et al. compare structures of the cation channel TRPM4 "frozen" at 4 °C versus 37 °C, revealing how temperature critically affects the binding of activating Ca ²⁺ ions and other channel modulators.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thomas Voets reports financial support was provided by Research Foundation Flanders. Brett Boonen reports financial support was provided by Research Foundation Flanders. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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