An analysis of oligomerization interfaces in transmembrane proteins

Area of Science:

• Structural biology
• Biochemistry
• Membrane protein analysis

Background:

• A growing number of transmembrane protein structures allows for large-scale interface analysis.
• Investigating oligomeric interfaces within the transmembrane region is now feasible.

Purpose of the Study:

• To compile and analyze a comprehensive set of validated transmembrane protein interfaces.
• To compare transmembrane protein interfaces with those of soluble proteins.
• To evaluate the biological relevance of proposed G protein-coupled receptor (GPCR) dimer interfaces.

Main Methods:

• Compilation of a validated dataset of transmembrane protein interfaces.
• Comparative analysis of interface features (size, packing, core residues).
• Assessment of proposed GPCR dimer interfaces from crystallographic data.

Main Results:

• Transmembrane protein interfaces exhibit characteristics similar to soluble proteins, including large size and tight packing.
• Membrane lipids were not found to be significant mediators of protein-protein interfaces in the studied set.
• Putative dimer interfaces for class A GPCRs lack hallmarks of stable biological interactions, suggesting they are likely crystal artifacts.

Conclusions:

• Transmembrane protein interfaces are generally similar to soluble protein interfaces.
• Crystal interfaces of class A GPCRs are unlikely to represent stable biological interactions.
• The human Smoothened receptor (class F) dimer shows evidence of a biological interface.