PxxPcontaining

PxxP-containing refers to proteins or peptide regions that include a PxxP motif, where two proline residues are separated by any two amino acids (P-X-X-P). This short linear motif is a hallmark of many signaling and cytoskeletal proteins and is recognized by SH3 domains in a variety ofinteraction partners.

The binding between PxxP motifs and SH3 domains is a key mechanism for assembling signaling complexes. SH3 domains bind to proline-rich sequences in partner proteins, facilitating recruitment and organization of enzymes, adaptors, and structural proteins at membranes or along the cytoskeleton. The interaction is typically of moderate affinity but highly specific, enabling dynamic regulation of signaling networks.

Structural context helps explain binding affinity. PxxP motifs often adopt a polyproline II helix that fits the SH3 domain groove. The surrounding sequence and the conformational state of the motif can modulate binding strength and partner selectivity. Post-translational modifications, alternative splicing, and prolyl isomerization can further regulate these interactions, adding layers of control to signaling and trafficking pathways.

PxxP motifs are widespread in many classes of proteins, including receptors, adaptor proteins, and cytoskeletal regulators. Notable examples include SOS1, which contains PxxP-rich regions that bind Grb2 SH3 domains, and Crk and Nck family adaptors that relay signals through SH3-mediated interactions. Because of their prevalence and modular nature, PxxP-containing regions are often used to map protein–protein interaction networks and to understand the assembly of signaling complexes.