Structure of the bifunctional and Golgi-associated formiminotransferase cyclodeaminase octamer.
Mammalian formiminotransferase cyclodeaminase (FTCD), a 0.5 million Dalton homo-octameric enzyme, plays important roles in coupling histidine catabolism with folate metabolism and integrating the Golgi complex with the vimentin intermediate filament cytoskeleton. It is also linked to two human diseases, autoimmune hepatitis and glutamate formiminotransferase deficiency. Determination of the FTCD structure by X-ray crystallography and electron cryomicroscopy revealed that the eight subunits, each composed of distinct FT and CD domains, are arranged like a square doughnut. A key finding indicates that coupling of three subunits governs the octamer-dependent sequential enzyme activities, including channeling of intermediate and conformational change. The structure further shed light on the molecular nature of two strong antigenic determinants of FTCD recognized by autoantibodies from patients with autoimmune hepatitis and on the binding of thin vimentin filaments to the FTCD octamer.
Mao
Yuxin
Y
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA.
Vyas
Nand K
NK
Vyas
Meenakshi N
MN
Chen
Dong-Hua
DH
Ludtke
Steven J
SJ
Chiu
Wah
W
Quiocho
Florante A
FA
D000595:Amino Acid Sequence; D000642:Ammonia-Lyases / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000276:immunology; D006056:Golgi Apparatus / Q000201:enzymology*; D006505:Hepatitis / Q000276:immunology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009068:Movement; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D014746:Vimentin / Q000737:chemistry / Q000378:metabolism
D001324:Autoantigens; D000939:Epitopes; D021122:Protein Subunits; D014746:Vimentin; D000642:Ammonia-Lyases; C500814:Ftcd protein, rat; C020148:formiminotetrahydrofolate cyclodeaminase