The tandem Src homology 2 domain of the Syk kinase: a molecular device that adapts to interphosphotyrosine distances.
Conformational flexibility is important for protein function. However, information on the range of conformations accessible to macromolecules in the unbound state is often difficult to obtain. By using the model system of the tandem Src homology 2 domain (i.e., two adjacent Src homology 2 domains) of the Syk kinase, we report a method combining calorimetric and crystallographic measurements that reveals the preexistence of a conformational equilibrium in the unbound state, and that shows that this equilibrium is crucial for function.
Kumaran
Sangaralingam
S
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, MO 63110, USA.
Grucza
Richard A
RA
Waksman
Gabriel
G
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry; D002151:Calorimetry; D018360:Crystallography, X-Ray; D004229:Dithiothreitol / Q000494:pharmacology; D004792:Enzyme Precursors / Q000737:chemistry*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry; D019000:Phosphotyrosine / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D017452:Receptors, IgG / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013050:Spectrometry, Fluorescence; D000072377:Syk Kinase; D013816:Thermodynamics; D018909:src Homology Domains
D015703:Antigens, CD; D004792:Enzyme Precursors; C080568:Fc gamma receptor IIA; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D010455:Peptides; D017452:Receptors, IgG; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D004229:Dithiothreitol