Structure of the connexin 26 gap junction channel at 3.5 Å resolution

  title={Structure of the connexin 26 gap junction channel at 3.5 {\AA} resolution},
  author={Shoji Maeda and So Nakagawa and Michihiro Suga and Eiki Yamashita and Atsunori Oshima and Yoshinori Fujiyoshi and Tomitake Tsukihara},
Gap junctions consist of arrays of intercellular channels between adjacent cells that permit the exchange of ions and small molecules. Here we report the crystal structure of the gap junction channel formed by human connexin 26 (Cx26, also known as GJB2) at 3.5 Å resolution, and discuss structural determinants of solute transport through the channel. The density map showed the two membrane-spanning hemichannels and the arrangement of the four transmembrane helices of the six protomers forming… 

Structure of the connexin-43 gap junction channel reveals a closed sieve-like molecular gate

The structure of a human Cx43 GJC solved by cryo-EM and single particle analysis at 2.26 Å resolution is described and a previously undescribed closed sieve-like gate is found on the cytosolic side of the pore, formed by the N-terminal domain and the transmembrane helix 2 of Cx 43 and stabilized by a small molecule.

Charge at the 46th residue of connexin 50 is crucial for the gap‐junctional unitary conductance and transjunctional voltage‐dependent gating

The results indicate that the pore surface electrostatic potential is a dictating factor for the connexin 50 GJ channel γj, and a change in the local resistance of the channel pore associated with these mutant channels is an important factor for their voltage‐dependent gating properties.

Structural insights into the gating mechanism of human Cx43/GJA1 gap junction channel

Cryo-EM structures of Cx43 GJIChs at 3.1–3.6 Å resolutions are reported, which show dynamic conformational changes of N-terminal helices (NTHs) caused by pH change or C-terminals truncation, and structural insights into the intercellular ion/metabolite transfer and the lateral lipid transport are provided.

Gap junction structure: unraveled, but not fully revealed

High-resolution structures and modeling of other connexin channels will be required to account for the diverse biophysical properties and regulation conferred by the differences in their sequences to allow an atomic-level understanding of intercellular communication mediated by Connexin26.

Structure of the gap junction channel and its implications for its biological functions

A number of studies have tried to reveal the molecular architecture of the channel pore that should confer the connexin-specific permeability/selectivity properties and molecular basis for the gating and regulation of gap junction channels.

Atomic structure of the innexin-6 gap junction channel determined by cryo-EM

Cryo-electron microscopy structures of Caenorhabditis elegans innexin-6 (INX-6) gap junction channels at atomic resolution find that the arrangements of the transmembrane helices and extracellular loops of the INx-6 monomeric structure are highly similar to those of con Nexin-26 (Cx26), despite the lack of significant sequence similarity.

Structure and closure of connexin gap junction channels




Three-dimensional structure of a human connexin26 gap junction channel reveals a plug in the vestibule

The electron crystallographic structure of a human Cx26 mutant (M34A) is reported to suggest that the two docked hemichannels can be independent and may regulate their activity autonomously with a plug in the vestibule.

Three-dimensional structure of a recombinant gap junction membrane channel.

Although not indicative for a particular type of secondary structure, the protein density that formed the extracellular vestibule provided a tight seal to exclude the exchange of substances with theextracellular milieu.

Identification of a proline residue as a transduction element involved in voltage gating of gap junctions

A strictly conserved proline centrally located in M2 of connexin proteins is examined, which suggests that the unique properties associated with this residue are critical to the transduction of voltage gating in these channels.

Identification of amino acid residues lining the pore of a gap junction channel

The pore-lining residues of a gap junction channel composed of Cx32 are identified, indicating that the selective permeabilities of this unique channel class may result from novel mechanisms, including complex van der Waals interactions of permeants with the pore wall, rather than mechanisms involving fixed charges or chelation chemistry as reported for other ion channels.

Projection Structure of a N-Terminal Deletion Mutant of Connexin 26 Channel with Decreased Central Pore Density

The difference map between the deletion and full-length Cx26M34A channels strongly suggests that the N-terminus of connexin contributes to the plug for the physical closure of gap junction channels.

Conformational changes in surface structures of isolated connexin 26 gap junctions

Using atomic force microscopy (AFM), conformational changes of the cytoplasmic and extracellular surfaces of native connexin 26 gap junction plaques suggest that calcium ions induce conformationalChanges affecting the structure of both the hemichannels and the intact channels forming cell–cell contacts.

Structure of the amino terminus of a gap junction protein.

It is reported that intercellular channels containing mutations of G12 in Cx32 to residues that are likely to interfere with flexibility of this locus do not express junctional currents, whereas a connexin containing a proline residue at G12 (Cx32G12P), which is expected to maintain a structure similar to that of the G12 locus, forms nearly wild-type channels.

Size Selectivity Between Gap Junction Channels Composed of Different Connexins

A graded series of neutral polyethylene glycol probes (PEGs), which eliminate charge contribution completely, are used to specifically assess the physical exclusion limits of gap junction channels formed by different connexins.

Opposite voltage gating polarities of two closely related onnexins

A consistent correlation between charge substitu-tion and gating polarity indicates that Cx26 and Cx32 voltage sensors are oppositely charged and that both move towards the cytoplasm upon hemichannel closure.