Transmembrane signalling and the aspartate receptor

Area of Science:

• Biochemistry
• Structural Biology
• Microbiology

Background:

• The aspartate receptor is a transmembrane protein crucial for bacterial chemotaxis.
• Previous structures revealed the ligand-binding domain but excluded transmembrane regions.
• Aspartate binds at the subunit interface within the periplasmic domain.

Purpose of the Study:

• To investigate the structure of the aspartate receptor's transmembrane region.
• To model the coiled-coil structure of the transmembrane helices.
• To understand the mechanism of signal transduction in this receptor.

Main Methods:

• Constructed a mutant protein with cross-links to stabilize the subunit interface.
• Developed an energy-minimized model of the transmembrane region.
• Integrated ligand-binding domains with amino-terminal transmembrane helices.

Main Results:

• Demonstrated that transmembrane helices form a continuous coiled coil from the periplasmic side through the membrane.
• The coiled-coil structure restrains the subunit-subunit interface on both sides of the membrane.
• A model of the ligand-binding domains connected to transmembrane helices was created.

Conclusions:

• The intact receptor features an uninterrupted coiled coil at the subunit interface.
• This coiled-coil structure excludes several proposed signaling mechanisms.
• Signal transduction likely involves long-range propagation of small, low-energy conformational changes in side chains.