Three-dimensional structure of a human connexin26 gap junction channel reveals a plug in the vestibule
- 12 June 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (24), 10034-10039
- https://doi.org/10.1073/pnas.0703704104
Abstract
Connexin molecules form intercellular membrane channels facilitating electronic coupling and the passage of small molecules between adjoining cells. Connexin26 (Cx26) is the second smallest member of the gap junction protein family, and mutations in Cx26 cause certain hereditary human diseases such as skin disorders and hearing loss. Here, we report the electron crystallographic structure of a human Cx26 mutant (M34A). Although crystallization trials used hemichannel preparations, the density map revealed that two hemichannels redocked at their extracellular surfaces into full intercellular channels. These orthorhombic crystals contained two sets of symmetry-related intercellular channels within three lipid bilayers. The 3D map shows a prominent density in the pore of each hemichannel. This density contacts the innermost helices of the surrounding connexin subunits at the bottom of the vestibule. The density map suggests that physical blocking may play an important role that underlies gap junction channel regulation. Our structure allows us to suggest that the two docked hemichannels can be independent and may regulate their activity autonomously with a plug in the vestibule.Keywords
This publication has 37 references indexed in Scilit:
- Pathogenetic role of the deafness-related M34T mutation of Cx26Human Molecular Genetics, 2006
- Structural bases for the chemical regulation of Connexin43 channelsCardiovascular Research, 2004
- Chemical gating of gap junction channels: Roles of calcium, pH and calmodulinBiochimica et Biophysica Acta (BBA) - Biomembranes, 2004
- Identification of amino acid residues lining the pore of a gap junction channelThe Journal of cell biology, 2002
- Connexin Mutations in Skin Disease and Hearing LossAmerican Journal of Human Genetics, 2001
- Stoichiometry of Transjunctional Voltage–Gating Polarity Reversal by a Negative Charge Substitution in the Amino Terminus of a Connexin32 ChimeraThe Journal of general physiology, 2000
- Opposite voltage gating polarities of two closely related onnexinsNature, 1994
- Structural Elements Involved in Specific K+ Channel FunctionsAnnual Review of Physiology, 1992
- Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopyJournal of Molecular Biology, 1990
- Structure of the junction between communicating cellsNature, 1980