Cloning, expression, crystallization and initial crystallographic analysis of the C-terminal domain of the amyloid precursor protein APP.
Alzheimer's disease is associated with typical brain deposits (senile plaques) consisting mainly of neurotoxic amyloid beta-peptides. These are proteolytically derived from the large type I transmembrane protein amyloid precursor protein (APP), which is possibly involved in signal transduction. The large C-terminal domain CAPPD of the human APP ectodomain has been cloned, expressed in large amounts in Escherichia coli and purified to homogeneity. Well diffracting tetragonal crystals have been obtained and native data have been collected to 2.1 A. Initial experimental phases from a three-wavelength MAD experiment using (NH(4))(2)OsCl(6)-derivatized crystals are of good quality and show mostly alpha-helical conformations.
Keil
Cora
C
Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18A, 82152 Martinsried, Germany.
Huber
Robert
R
Bode
Wolfram
W
Than
Manuel E
ME
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D003001:Cloning, Molecular; D003460:Crystallization; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003627:Data Interpretation, Statistical; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D014961:X-Ray Diffraction
D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary