G protein-coupled odorant receptors: From sequence to structure.

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Odorant receptors (ORs) represent the largest subfamily of class A G protein-coupled receptors (GPCRs).
• Experimental structural data for ORs is currently unavailable, hindering detailed mechanistic understanding.
• Molecular modeling approaches are crucial for gaining atomic-level insights into OR structure and function.

Purpose of the Study:

• To critically align OR sequences with known GPCR structures.
• To propose a sequence alignment consistent with site-directed mutagenesis data for ORs.
• To assess the impact of template choice in molecular modeling of ORs.

Main Methods:

• Sequence alignment of Odorant Receptors (ORs) with G protein-coupled receptors (GPCRs) of known structure.
• Integration of available site-directed mutagenesis data to refine the alignment.
• Comparative analysis of molecular modeling outcomes based on different structural templates.

Main Results:

• A refined sequence alignment for ORs, validated by mutagenesis data, is presented.
• The proposed alignment facilitates the identification of residues forming the odorant binding cavity.
• Residues critical for G protein interaction can be identified irrespective of the specific template used.

Conclusions:

• Sequence alignment with known GPCRs is a viable strategy for modeling ORs.
• The proposed alignment aids in understanding OR structure-function relationships.
• Molecular modeling of ORs can provide valuable insights despite the lack of experimental structures.