3D structure of Syk kinase determined by single-particle electron microscopy.
The cytoplasmic Syk kinase plays key roles in immune responses and comprises two N-terminal regulatory Src homology 2 (SH2) domains followed by a catalytic region. Atomic structures of these domains have only been solved in isolation. To gain insights into the three-dimensional structure of full-length Syk, we have used single-particle electron microscopy. Syk acquires a closed conformation resembling the inhibited structure of Zap-70, another member of the Syk family. Such configuration suggests an inhibition of the N-terminal domains on its catalytic activity. The phosphotyrosine binding pockets of both SH2 domains are not occluded and they could interact with other phosphoproteins.
Arias-Palomo
Ernesto
E
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (Spanish National Research Council, CSIC), Ramiro de Maeztu, 9, E28040 Madrid, Spain.
Recuero-Checa
María A
MA
Bustelo
Xosé R
XR
Llorca
Oscar
O
D000818:Animals; D021621:Imaging, Three-Dimensional; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology; D008854:Microscopy, Electron / Q000379:methods*; D008958:Models, Molecular; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology; D051381:Rats; D000072377:Syk Kinase
D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat