ORIGINAL RESEARCH article
Front. Biophys.
Sec. Protein Structure and Dynamics
Volume 3 - 2025 | doi: 10.3389/frbis.2025.1569091
This article is part of the Research TopicDecoding Ion Channels: From Biophysics to Cellular Function and PharmacologyView all articles
Interaction studies between Calmodulin and Gating Brake Peptides from T-Type Channels
Provisionally accepted
Shivani Yaduvanshi
Veerendra Kumar*- Amity Institute of Molecular Medicine & Stem Cell Research, Amity University, Noida, India
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The voltage gated calcium channels (Cav1 and Cav2) and sodium channels are modulated by calmodulin (CaM) via IQ motifs. But Cav3 (aka T-type) channels lack IQ motif and therefore, they transiently interact with CaM via the gating brake (GB) regions of T-type channels.However, the structural basis of the interactions remains unclear. This study employs molecular dynamics (MD) simulations to investigate the complete binding process of GB peptides (GB3.1 and GB3.2) with CaM at an atomic level, starting from a non-interacting state to a fully formed complex. We provide a detailed analysis of the binding trajectories, identifying how the GB peptides dynamically explore and engage their binding interfaces on CaM. Our results reveal that GB3.1 induces significant conformational rearrangement in CaM, bending its central helix by ~90° and forming a compact structure. In contrast, GB3.2 binding does not induce such changes, and CaM remains in an extended conformation. Both peptides interact primarily with CaM's N-lobe. The MM-PBSA analysis yielded negative binding energies indicating a spontaneous and favourable complex formation.
Keywords: Calmodulin, Gating brake, T-type ion channels, Cav3.1, Cav3.2, MD simulations
Received: 31 Jan 2025; Accepted: 12 May 2025.
Copyright: © 2025 Yaduvanshi and Kumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Veerendra Kumar, Amity Institute of Molecular Medicine & Stem Cell Research, Amity University, Noida, India
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