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Reply to ‘Concerns with yeast mitochondrial ADP/ATP carrier’s integrity in DPC’ and ‘Dynamics and interactions of AAC3 in DPC are not functionally relevant’

Nature Structural & Molecular Biology volume 25, pages 749–750 (2018)Cite this article

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Yang et al. reply: In their correspondence, Kurauskas et al.1 and King et al.2 claim that the protein we used to measure the micro- to millisecond dynamics of yeast ADP/ATP carrier (yAAC3) in our NSMB study3 was not in a functional, native state and thus the data have no biological relevance.

We strongly believe that yAAC3 in dodecylphosphocholine (DPC), although suboptimally folded and unable to generate a native dissociation constant (K d) for ligand CATR, is nevertheless in a state that can provide qualitative information that is relevant for functional investigations. A suboptimally folded state is in many ways expected for detergent-solubilized membrane proteins; the detergent could have loosened the structure, effectively making the ligand-binding site more dynamic. Even minor destabilization of the binding site can have a dramatic effect on K d. The key question is, can we learn anything meaningful from the yAAC3 sample used for NMR analyses? NMR allows direct K d measurements, but this does not mean that a sample must have physiological K d to be considered suitable for structural investigations.

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References

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Author notes

  1. Qin Yang

    Present address: Aptitude Medical Systems, Inc., Santa Barbara, CA, USA

  2. Sven Brüschweiler

    Present address: Department for Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria

  3. These authors contributed equally: Qin Yang, Sven Brüschweiler.

Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

    Qin Yang, Sven Brüschweiler, Linlin Zhao & James J. Chou

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  1. Qin Yang
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  2. Sven Brüschweiler
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Correspondence to James J. Chou.

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Yang, Q., Brüschweiler, S., Zhao, L. et al. Reply to ‘Concerns with yeast mitochondrial ADP/ATP carrier’s integrity in DPC’ and ‘Dynamics and interactions of AAC3 in DPC are not functionally relevant’. Nat Struct Mol Biol 25, 749–750 (2018). https://doi.org/10.1038/s41594-018-0126-5

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