Structure of the PTB domain of tensin1.
|PTB domain (IRS-1 type)|
irs-1 ptb domain complexed with a il-4 receptor phosphopeptide, nmr, minimized average structure
The phosphotyrosine-binding domain (PTB, also phosphotyrosine-interaction or PI domain) in the protein tensin tends to be found at the C-terminus. Tensin is a multi-domain protein that binds to actin filaments and functions as a focal-adhesion molecule (focal adhesions are regions of plasma membrane through which cells attach to the extracellular matrix). Human tensin has actin-binding sites, an SH2 (Pfam PF00017) domain and a region similar to the tumour suppressor PTEN. The PTB domain interacts with the cytoplasmic tails of beta integrin by binding to an NPXY motif.
The phosphotyrosine-binding domain of insulin receptor substrate-1 is not related to the phosphotyrosine-binding domain of tensin. Insulin receptor substrate-1 proteins contain both a pleckstrin homology domain and a phosphotyrosine binding (PTB) domain. The PTB domains facilitate interaction with the activated tyrosine-phosphorylated insulin receptor. The PTB domain is situated towards the N terminus. Two arginines in this domain are responsible for hydrogen bonding phosphotyrosine residues on an Ac-LYASSNPApY-NH2 peptide in the juxtamembrane region of the insulin receptor. Further interactions via "bridged" water molecules are coordinated by residues an Asn and a Ser residue. The PTB domain has a compact, 7-stranded beta-sandwich structure, capped by a C-terminal helix. The substrate peptide fits into an L-shaped surface cleft formed from the C-terminal helix and strands 5 and 6.
Human proteins containing these domains
- SH2 domains also bind phosphorylated tyrosines
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- Zhou MM, Huang B, Olejniczak ET, Meadows RP, Shuker SB, Miyazaki M, Trub T, Shoelson SE, Fesik SW (April 1996). "Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain". Nat. Struct. Biol. 3 (4): 388–93. doi:10.1038/nsb0496-388. PMID 8599766.
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