title: Structure basis for the regulation of glyceraldehyde-3-phosphate dehydrogenase activity via the intrinsically disordered protein CP12.
abstract: The reversible formation of a glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-CP12-phosphoribulokinase (PRK) supramolecular complex, identified in oxygenic photosynthetic organisms, provides light-dependent Calvin cycle regulation in a coordinated manner. An intrinsically disordered protein (IDP) CP12 acts as a linker to sequentially bind GAPDH and PRK to downregulate both enzymes. Here, we report the crystal structures of the ternary GAPDH-CP12-NAD and binary GAPDH-NAD complexes from Synechococcus elongates. The GAPDH-CP12 complex structure reveals that the oxidized CP12 becomes partially structured upon GAPDH binding. The C-terminus of CP12 is inserted into the active-site region of GAPDH, resulting in competitive inhibition of GAPDH. This study also provides insight into how the GAPDH-CP12 complex is dissociated by a high NADP(H)/NAD(H) ratio. An unexpected increase in negative charge potential that emerged upon CP12 binding highlights the biological function of CP12 in the sequential assembly of the supramolecular complex.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. matsumura@chem.eng.osaka-u.ac.jp
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Matsumura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Maeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tamoi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Satoh
authors.forename: Haruka
authors.initials: H
authors.lastname: Tamura
authors.forename: Mika
authors.initials: M
authors.lastname: Hirose
authors.forename: Taketo
authors.initials: T
authors.lastname: Ogawa
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kizu
authors.forename: Akira
authors.initials: A
authors.lastname: Wadano
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Shigeru
authors.initials: S
authors.lastname: Shigeoka
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D046940:Synechococcus / Q000201:enzymology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D046912:Multiprotein Complexes; D009243:NAD; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases