D
IPR006020

PTB/PI domain

InterPro entry
Short namePTB/PI_dom
Overlapping
homologous
superfamilies
 
domain relationships

Description

Proteins encoding phosphotyrosine binding (PTB) domains function as adaptors or scaffolds to organise the signaling complexes involved in wide-ranging physiological processes including neural development, immunity, tissue homeostasis and cell growth. Due to structural differences, PTB domains are divided into three groups represented by phosphotyrosine-dependent IRS-like, phosphotyrosine-dependent Shc-like, and phosphotyrosine-independent Dab-like PTBs. The last two PTBs have been named as phosphotyrosine interaction domain (PID or PI domain). PID domain has an average length of about 160 amino acids
[3]
.

The Shc-like PID specifically binds to the Asn-Pro-Xaa-Tyr(P) motif found in many tyrosine-phosphorylated proteins including growth factor receptors. On the other hand the Dab-like PID domain binds to non-phosphorylated tyrosine residue or even a phenylalanine at the same position
[2]
. Most of the ligands for Shc-like PID domains are RTK or cytokine, whereas phosphotyrosine independent Dab-like PID domains seems to mediate other types of signaling pathways, like endocytosis/processing or exocytosis. This domain binds both peptides and headgroups of phosphatidylinositides, utilising two distinct binding motifs to mediate spatial organisation and localisation within cells
[3, 2, 1, 5]
.

The 3D structure of PID domain has been solved
[4]
. It shares a folding pattern, commonly referred to as the PH-domain "superfold". The core "superfold" consists of seven antiparallel β strands forming two orthogonal β sheets. This β sandwich is capped at the C terminus by an α helix. It contains a peptide binding pocket (formed by the β strand 5 and C-terminal α helix) and a highly basic phospholipid binding "crown" (largely composed of residues from loop regions near the N terminus). Both Shc and Dab1 have two additional α helices, one of which is located at the N terminus and the other between β1 and β2 strands.

References

1.An alternative to SH2 domains for binding tyrosine-phosphorylated proteins. Kavanaugh WM, Williams LT. Science 266, 1862-5, (1994). View articlePMID: 7527937

2.A phosphotyrosine interaction domain. Bork P, Margolis B. Cell 80, 693-4, (1995). View articlePMID: 7534213

3.Structural and evolutionary division of phosphotyrosine binding (PTB) domains. Uhlik MT, Temple B, Bencharit S, Kimple AJ, Siderovski DP, Johnson GL. J. Mol. Biol. 345, 1-20, (2005). View articlePMID: 15567406

4.Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes. Stolt PC, Jeon H, Song HK, Herz J, Eck MJ, Blacklow SC. Structure 11, 569-79, (2003). View articlePMID: 12737822

5.A region in Shc distinct from the SH2 domain can bind tyrosine-phosphorylated growth factor receptors. Blaikie P, Immanuel D, Wu J, Li N, Yajnik V, Margolis B. J. Biol. Chem. 269, 32031-4, (1994). View articlePMID: 7798194

Cross References

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