TPRdomaincontaining

TPR domain-containing proteins are a diverse group defined by the presence of tetratricopeptide repeats (TPR), modular motifs of about 34 amino acids that commonly mediate protein-protein interactions. Individual TPR motifs fold into two alpha-helices, and several repeats stack into a superhelical structure that presents a binding groove for partner proteins. The number and arrangement of repeats vary, producing a wide range of binding specificities and enabling the assembly of multiprotein complexes.

Functions of these proteins are typically as scaffolds or adaptors that coordinate large protein assemblies. They participate in chaperone networks, particularly involving Hsp70 and Hsp90 chaperones, and are also implicated in mitochondrial protein import, cytoskeletal organization, and trafficking between organelles. Beyond protein folding and transport, TPR-containing proteins contribute to signaling pathways and the assembly of complexes involved in transcription, ubiquitination, and ribosome biogenesis.

Examples and families: The Hsp70/Hsp90 organizing protein Hop, or Sti1, is a classic TPR-containing cochaperone that binds both chaperones via distinct TPR motifs. The tetratricopeptide repeat-containing (TTC) protein family represents a large subset of TPR-domain proteins in eukaryotes, with members often having tissue- or development-specific roles. TPR repeats are also found in bacterial and archaeal proteins, reflecting their broad role in protein interaction networks.

Identification and research: TPR domain-containing proteins are identified by conserved motifs detected through sequence analysis in databases such as Pfam and InterPro. Structural studies reveal elongated solenoids, while functional characterization typically relies on protein-protein interaction assays and co-immunoprecipitation to map binding partners.