Structure and ligand recognition of the phosphotyrosine binding domain of Shc.
The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of Shc complexed to a phosphopeptide reveals an alternative means of recognizing tyrosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel beta-strand with a beta-sheet of the protein, interacts with a hydrophobic pocket through the (pY-5) residue, and adopts a beta-turn. The PTB domain is structurally similar to pleckstrin homology domains (a beta-sandwich capped by an alpha-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization.
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
M M
MM
Zhou
K S
KS
Ravichandran
E F
EF
Olejniczak
A M
AM
Petros
R P
RP
Meadows
M
M
Sattler
J E
JE
Harlan
W S
WS
Wade
S J
SJ
Burakoff
S W
SW
Fesik
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins; D019000:Phosphotyrosine / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D001798:Blood Proteins; D008024:Ligands; D010446:Peptide Fragments; D010743:Phospholipids; D010748:Phosphopeptides; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D055765:Shc Signaling Adaptor Proteins; C039077:platelet protein P47; D019000:Phosphotyrosine; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA