Immunocytochemical Localization and Crystal Structure of Human Frequenin (Neuronal Calcium Sensor 1)

Yves Bourne (1) , Jens Dannenberg (2) , Verena Pollmann (2) , Pascale Marchot (3) , Olaf Pongs (2)

1 AFMB - Architecture et fonction des Macromolécules Biologiques - UMR 6098
2 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
3 Biochimie - Ingénierie des protéines

Frequenin, a member of a large family of myristoylswitch calcium-binding proteins, functions as a calciumion sensor to modulate synaptic activity and secretion. We show that human frequenin colocalizes with ARF1 GTPase in COS-7 cells and occurs in similar cellular compartments as the phosphatidylinositol-4-OH kinase PI4K␤, the mammalian homolog of the yeast kinase PIK1. In addition, the crystal structure of unmyristoylated, calcium-bound human frequenin has been determined and refined to 1.9 Å resolution. The overall fold of frequenin resembles those of neurocalcin and the photoreceptor, recoverin, of the same family, with two pairs of calcium-binding EF hands and three bound calcium ions. Despite the similarities, however, frequenin displays significant structural differences. A large conformational shift of the C-terminal region creates a wide hydrophobic crevice at the surface of frequenin. This crevice, which is unique to frequenin and distinct from the myristoyl-binding box of recoverin, may accommodate a yet unknown protein ligand.

Domaines: Sciences du Vivant [q-bio]

Yves Bourne, Jens Dannenberg, Verena Pollmann, Pascale Marchot, Olaf Pongs. Immunocytochemical Localization and Crystal Structure of Human Frequenin (Neuronal Calcium Sensor 1). Journal of Biological Chemistry, 2000, 276, pp.11949 - 11955. ⟨10.1074/jbc.m009373200⟩. ⟨hal-03263149⟩