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Structure of the bifunctional and Golgi‐associated formiminotransferase cyclodeaminase octamer
Author(s) -
Mao Yuxin,
Vyas Nand K,
Vyas Meenakshi N,
Chen DongHua,
Ludtke Steven J,
Chiu Wah,
Quiocho Florante A
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600327
Subject(s) - biology , bifunctional , histone octamer , golgi apparatus , microbiology and biotechnology , genetics , biochemistry , endoplasmic reticulum , gene , histone , nucleosome , catalysis
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.