Person:
DeCaen, Paul

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

DeCaen

First Name

Paul

Name

DeCaen, Paul
Author's Publications: search.filters.isAuthorOfPublication.59569a61-8605-41a8-8057-accf082df750

Search Results

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Role of the C-terminal domain in the structure and function of tetrameric sodium channels
    (Nature Pub. Group, 2013) Bagnéris, Claire; DeCaen, Paul; Hall, Benjamin A.; Naylor, Claire E.; Clapham, David; Kay, Christopher W. M.; Wallace, B. A.
    Voltage-gated sodium channels have essential roles in electrical signalling. Prokaryotic sodium channels are tetramers consisting of transmembrane (TM) voltage-sensing and pore domains, and a cytoplasmic carboxy-terminal domain. Previous crystal structures of bacterial sodium channels revealed the nature of their TM domains but not their C-terminal domains (CTDs). Here, using electron paramagnetic resonance (EPR) spectroscopy combined with molecular dynamics, we show that the CTD of the NavMs channel from Magnetococcus marinus includes a flexible region linking the TM domains to a four-helix coiled-coil bundle. A 2.9 Å resolution crystal structure of the NavMs pore indicates the position of the CTD, which is consistent with the EPR-derived structure. Functional analyses demonstrate that the coiled-coil domain couples inactivation with channel opening, and is enabled by negatively charged residues in the linker region. A mechanism for gating is proposed based on the structure, whereby splaying of the bottom of the pore is possible without requiring unravelling of the coiled-coil.
  • Thumbnail Image
    Publication
    Atypical calcium regulation of the PKD2-L1 polycystin ion channel
    (eLife Sciences Publications, Ltd, 2016) DeCaen, Paul; Liu, Xiaowen; Abiria, Sunday; Clapham, David
    Native PKD2-L1 channel subunits are present in primary cilia and other restricted cellular spaces. Here we investigate the mechanism for the channel's unusual regulation by external calcium, and rationalize this behavior to its specialized function. We report that the human PKD2-L1 selectivity filter is partially selective to calcium ions (Ca2+) moving into the cell, but blocked by high internal Ca2+concentrations, a unique feature of this transient receptor potential (TRP) channel family member. Surprisingly, we find that the C-terminal EF-hands and coiled-coil domains do not contribute to PKD2-L1 Ca2+-induced potentiation and inactivation. We propose a model in which prolonged channel activity results in calcium accumulation, triggering outward-moving Ca2+ ions to block PKD2-L1 in a high-affinity interaction with the innermost acidic residue (D523) of the selectivity filter and subsequent long-term channel inactivation. This response rectifies Ca2+ flow, enabling Ca2+ to enter but not leave small compartments such as the cilium. DOI: http://dx.doi.org/10.7554/eLife.13413.001
  • Thumbnail Image
    Publication
    Molecular basis of ion permeability in a voltage‐gated sodium channel
    (John Wiley and Sons Inc., 2016) Naylor, Claire E; Bagnéris, Claire; DeCaen, Paul; Sula, Altin; Scaglione, Antonella; Clapham, David; Wallace, BA
    Abstract Voltage‐gated sodium channels are essential for electrical signalling across cell membranes. They exhibit strong selectivities for sodium ions over other cations, enabling the finely tuned cascade of events associated with action potentials. This paper describes the ion permeability characteristics and the crystal structure of a prokaryotic sodium channel, showing for the first time the detailed locations of sodium ions in the selectivity filter of a sodium channel. Electrostatic calculations based on the structure are consistent with the relative cation permeability ratios (Na+ ≈ Li+ ≫ K+, Ca2+, Mg2+) measured for these channels. In an E178D selectivity filter mutant constructed to have altered ion selectivities, the sodium ion binding site nearest the extracellular side is missing. Unlike potassium ions in potassium channels, the sodium ions in these channels appear to be hydrated and are associated with side chains of the selectivity filter residues, rather than polypeptide backbones.