Immunocytochemical localization and crystal structure of human frequenin (neuronal calcium sensor 1).
Frequenin, a member of a large family of myristoyl-switch calcium-binding proteins, functions as a calcium-ion 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 PI4Kbeta, 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 A 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.
Bourne
Y
Y
Architecture et Fonction des Macromolécules Biologiques, CNRS UMR-6098, 13402, Marseille Cedex 20, France. yves@afmb.cnrs-mrs.fr
Dannenberg
J
J
Pollmann
V
V
Marchot
P
P
Pongs
O
O
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D018360:Crystallography, X-Ray; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins