Three-dimensional structure of the gap junction connexon

Area of Science:

• Cell biology
• Structural biology
• Biochemistry

Background:

• Gap junctions mediate direct intercellular transfer of ions and small molecules through connexons.
• Connexons, hexameric protein assemblies, form intercellular channels via extracellular interactions.
• Connexin protein family exhibits selectivity in channel formation and requires congruent interfaces for function.

Purpose of the Study:

• To determine the three-dimensional structure of a connexon.
• To investigate the structural asymmetry between extracellular and cytoplasmic domains of connexons.
• To understand the implications of hemichannel structure for unpaired connexons in plasma membranes.

Main Methods:

• Utilized a novel biochemical procedure to isolate ordered arrays of connexons from split gap junctions.
• Employed electron crystallographic methods for three-dimensional reconstruction of the connexon.
• Analyzed structural features of extracellular and cytoplasmic domains.

Main Results:

• A three-dimensional reconstruction of a connexon was successfully obtained.
• The reconstruction highlighted significant structural asymmetry between the extracellular and cytoplasmic domains.
• Distinct lobed structural features were assigned to the extracellular domains of the connexon.

Conclusions:

• The determined hemichannel structure provides insights into connexon organization.
• Structural asymmetry is a key feature of connexons, influencing their function.
• Findings have implications for understanding the role of unpaired connexons in cellular membranes.