Coupling of folding and binding in the PTB domain of the signaling protein Shc.
The notion that certain proteins lack intrinsic globular structure under physiological conditions and that the attainment of fully folded structure only occurs upon the binding of target molecules has been recently gaining popularity. We report here the solution structure of the PTB domain of the signaling protein Shc in the free form. Comparison of this structure with that of the complex form, obtained previously with a phosphopeptide ligand, reveals that the Shc PTB domain is structurally disordered in the free form, particularly around the regions constituting the peptide binding pocket. The binding of the ligand appears to reorganize this pocket through local folding events triggering a conformational switch between the free and the complex forms.
Farooq
Amjad
A
Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA. amjad.farooq@mssm.edu
Zeng
Lei
L
Yan
Kelley S
KS
Ravichandran
Kodi S
KS
Zhou
Ming-Ming
MM
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D019000:Phosphotyrosine / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D020033:Protein Isoforms / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D013059:Spectrum Analysis, Raman; D018909:src Homology Domains
D002352:Carrier Proteins; D008024:Ligands; D020033:Protein Isoforms; D011506:Proteins; D019000:Phosphotyrosine