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A distinct mechanism of C-type inactivation in the Kv-like KcsA mutant E71V

Author

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  • Ahmed Rohaim

    (The University of Chicago)

  • Bram J. A. Vermeulen

    (Utrecht University)

  • Jing Li

    (The University of Mississippi)

  • Felix Kümmerer

    (Utrecht University)

  • Federico Napoli

    (Utrecht University)

  • Lydia Blachowicz

    (The University of Chicago)

  • João Medeiros-Silva

    (Utrecht University)

  • Benoît Roux

    (The University of Chicago)

  • Markus Weingarth

    (Utrecht University)

Abstract

C-type inactivation is of great physiological importance in voltage-activated K+ channels (Kv), but its structural basis remains unresolved. Knowledge about C-type inactivation has been largely deduced from the bacterial K+ channel KcsA, whose selectivity filter constricts under inactivating conditions. However, the filter is highly sensitive to its molecular environment, which is different in Kv channels than in KcsA. In particular, a glutamic acid residue at position 71 along the pore helix in KcsA is substituted by a valine conserved in most Kv channels, suggesting that this side chain is a molecular determinant of function. Here, a combination of X-ray crystallography, solid-state NMR and MD simulations of the E71V KcsA mutant is undertaken to explore inactivation in this Kv-like construct. X-ray and ssNMR data show that the filter of the Kv-like mutant does not constrict under inactivating conditions. Rather, the filter adopts a conformation that is slightly narrowed and rigidified. On the other hand, MD simulations indicate that the constricted conformation can nonetheless be stably established in the mutant channel. Together, these findings suggest that the Kv-like KcsA mutant may be associated with different modes of C-type inactivation, showing that distinct filter environments entail distinct C-type inactivation mechanisms.

Suggested Citation

  • Ahmed Rohaim & Bram J. A. Vermeulen & Jing Li & Felix Kümmerer & Federico Napoli & Lydia Blachowicz & João Medeiros-Silva & Benoît Roux & Markus Weingarth, 2022. "A distinct mechanism of C-type inactivation in the Kv-like KcsA mutant E71V," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28866-9
    DOI: 10.1038/s41467-022-28866-9
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    References listed on IDEAS

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    1. Luis G. Cuello & Vishwanath Jogini & D. Marien Cortes & Albert C. Pan & Dominique G. Gagnon & Olivier Dalmas & Julio F. Cordero-Morales & Sudha Chakrapani & Benoît Roux & Eduardo Perozo, 2010. "Structural basis for the coupling between activation and inactivation gates in K+ channels," Nature, Nature, vol. 466(7303), pages 272-275, July.
    2. Yufeng Zhou & João H. Morais-Cabral & Amelia Kaufman & Roderick MacKinnon, 2001. "Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution," Nature, Nature, vol. 414(6859), pages 43-48, November.
    3. Chaowei Shi & Yao He & Kitty Hendriks & Bert L. de Groot & Xiaoying Cai & Changlin Tian & Adam Lange & Han Sun, 2018. "A single NaK channel conformation is not enough for non-selective ion conduction," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    4. Gary Yellen, 2002. "The voltage-gated potassium channels and their relatives," Nature, Nature, vol. 419(6902), pages 35-42, September.
    5. Adam Lange & Karin Giller & Sönke Hornig & Marie-France Martin-Eauclaire & Olaf Pongs & Stefan Becker & Marc Baldus, 2006. "Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR," Nature, Nature, vol. 440(7086), pages 959-962, April.
    6. Wojciech Kopec & Brad S. Rothberg & Bert L. Groot, 2019. "Molecular mechanism of a potassium channel gating through activation gate-selectivity filter coupling," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    7. Jared Ostmeyer & Sudha Chakrapani & Albert C. Pan & Eduardo Perozo & Benoît Roux, 2013. "Recovery from slow inactivation in K+ channels is controlled by water molecules," Nature, Nature, vol. 501(7465), pages 121-124, September.
    8. Simon Bernèche & Benoît Roux, 2001. "Energetics of ion conduction through the K+ channel," Nature, Nature, vol. 414(6859), pages 73-77, November.
    9. Luis G. Cuello & Vishwanath Jogini & D. Marien Cortes & Eduardo Perozo, 2010. "Structural mechanism of C-type inactivation in K+ channels," Nature, Nature, vol. 466(7303), pages 203-208, July.
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