Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways.
A broad range of organisms and tissues contain 14-3-3 proteins, which have been associated with many diverse functions including critical roles in signal transduction pathways, exocytosis and cell cycle regulation. We report here the crystal structure of the human T-cell 14-3-3 isoform (tau) dimer at 2.6 A resolution. Each monomer (Mr 28K) is composed of an unusual arrangement of nine antiparallel alpha-helices organized as two structural domains. The dimer creates a large, negatively charged channel approximately 35 A broad, 35 A wide and 20 A deep. Overall, invariant residues line the interior of this channel whereas the more variable residues are distributed on the outer surface. At the base of this channel is a 16-residue segment of 14-3-3 which has been implicated in the binding of 14-3-3 to protein kinase C.
Xiao
B
B
Division of Protein Structure, National Institute for Medical Research, Mill Hill, London, UK.
Smerdon
S J
SJ
Jones
D H
DH
Dodson
G G
GG
Soneji
Y
Y
Aitken
A
A
Gamblin
S J
SJ
D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D000818:Animals; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004926:Escherichia coli; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000737:chemistry; D014446:Tyrosine 3-Monooxygenase
D048948:14-3-3 Proteins; D011506:Proteins; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase