Protein Name

connexin-26 gap junction channel


Human (Homo sapiens)

Biological Context

The body of higher animals like human is composed of a huge number of cells and the intercellular communication is critically important for their biological activities. There are several means in the intercellular signaling, such as secreted molecules like hormone or neurotransmitter and its receptor, and adhesive molecules like cadherin or integrin. They areall mediated through membrane proteins. On the other hand, the gap junction is specialized membrane region where intercellular connecting channels called gap junction channels cluster. It is essential for the synchronous contraction of cardiomyocytes in hearts and keeping homeostasis for transparency in lens. A number of mutations in connexin genes, which encode transmembrane protein constituting gap junction channels, are associated with various human diseases.

In spite of the intensive structural studies by electron microscopy (EM) since its first finding, the structural detail of the gap junction channel has long been unknown, such as helical arrangement or the docking interactions. We have recently determined the atomic structure of human connexin26 (Cx26) gap junction channel by X-ray crystallography. The structure reveals the atomic basis for the organization and suggests the gating mechanism of it.

Structure Description


The observed channel is in the head-to-head docked state that spans two plasma membranes as an intercellular channel. The overall appearance is like that of tsuzumi, a traditional Japanese drum (Figure1).

Figure 1. Overall structure of Cx26 gap junction channel and its organization. The ribbon representations are Cx26 monomer, hexamer, and gap junction channel, respectively.

There is a central channel path along with the long axis of it, whose diameter is about 1.4nm at the narrowest point. The crystallographic analysis clearly shows the pore-lining residues, which will promote the functional studies on the different molecular permeability that each connexin has (Figure2).

Figure 2. Pore structure of the gap junction channel. (upper left) Amino acid residues that constitute the channel pore. (lower left) Sequence alignment of representative connexins showing the corresponding residues to pore-lining residues of Cx26. (right) Surface potential of Cx26 gap junction channel sectioned along the long axis, showing the pore interior.

The observed structure is in the open conformation. Recently, low resolution EM analysis has shown it in its closed conformation. The EM map shows a large electron density (plug) on the top of the pore, which is supposed to close the pore physically. In the X-ray atomic structure, there are six N-terminal helices forming a molecular funnel (Figure3).

Figure 3. (upper) Open conformation of the gap junction channel obtained by X-ray crystallography. (lower) Closed conformation of it obtained by EM analytsis. There is no obstruction that physically blocks the pore. The closed structure shows a large electron density in the channel entrance.

The previous studies suggested that the N-terminal region functions as a sensor for the trans-junctional voltage difference. Based on the functional studies and the two structures, we have proposed a model that the funnel undergoes conformational change and forms a plug to close the pore.

Protein Data Bank (PDB)



  • Maeda, S. Nakagawa, S. Suga, M. Yamashita, E. Oshima, A. Fujiyoshi, Y. Tsukihara, T.; "Structure of the connexin 26 gap junction channel at 3.5 A resolution"; Nature; (2009) 458:597-602 PubMed:19340074.


author: Shoji Maeda

Japanese version:PDB:2zw3