phosphothreoninebinding

Phosphothreoninebinding refers to the selective recognition of phosphorylated threonine residues by specific protein domains and motifs. Phosphorylation of threonine by kinases creates a negatively charged phosphate group that can be captured by dedicated phosphopeptide-binding pockets, often in the context of a surrounding sequence that influences affinity and specificity.

Key phosphothreonine-binding domains include FHA (forkhead-associated) domains, BRCT (BRCA1 C-terminal) domains, 14-3-3 proteins, and polo-box domains (PBD) of polo-like kinases. FHA domains specialize in binding phosphothreonine-containing motifs and play prominent roles in DNA damage signaling and cell cycle checkpoints. BRCT domains recognize phosphopeptides, frequently involved in the DNA damage response. 14-3-3 proteins are dimeric adaptors that bind both phosphoserine and phosphothreonine motifs across numerous substrates, regulating processes such as metabolism, transcription, and cell cycle control. Polo-box domains bind phosphopeptides containing phosphorylated residues near diagnostic motifs, aiding subcellular localization and activation of PLKs.

Binding mechanisms generally rely on electrostatic interactions between the phosphate group and positively charged residues in the binding pocket, complemented by hydrogen bonds and shape complementarity. The surrounding amino acids around pThr contribute to binding selectivity, so motif context is important for determining which proteins are recognized. Multivalency, conformational changes, and protein–protein interactions further modulate affinity and signaling outcomes.

Biological functions of phosphothreoninebinding include coordination of cell cycle progression, DNA damage response, signal transduction, and metabolic regulation. Regulation occurs through kinase and phosphatase activities, as well as via changes in protein conformation, localization, or complex formation that influence binding events.