Protein structure and function are critical components of cellular processes, and understanding the molecular mechanisms that regulate these processes is essential for developing new therapeutic interventions for protein-related diseases. The AXXXA and GXXXG motifs are important structural elements found in both membrane and globular proteins, playing diverse roles in regulating protein-protein interactions, stability, and function. These motifs are helical in nature and significantly contribute to the overall structure and function of proteins.

In membrane proteins, the AXXXA motif is crucial for the formation and maintenance of protein oligomers, while the GXXXG motif facilitates the formation of transmembrane dimers and oligomers. The CX-O interaction, involving a covalent bond between a cysteine residue and an oxygen atom, is more prevalent than previously understood and has been linked to protein stability, folding, and function.

Similarly, in globular proteins, the AXXXA and GXXXG motifs participate in protein-protein interactions, stability, and folding. The AXXXA motif acts as a hinge region allowing conformational changes, while the GXXXG motif contributes to the specificity of protein-protein interactions and the formation of dimers and oligomers. The helical nature of these motifs enables them to induce membrane curvature and regulate lipid-protein interactions in membrane proteins. In globular proteins, these motifs facilitate the formation of protein-protein interfaces and regulate conformational changes.

Investigating the AXXXA and GXXXG motifs, along with the CX-O interaction, provides a comprehensive understanding of the molecular mechanisms underlying protein structure and function in both membrane and globular proteins. This research has significant implications for developing new therapeutics, biomaterials, and designing drug delivery systems.

Keywords: protein-protein interaction; homodimers and heterodimers; helical motifs; gene ontology analysis