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  • The EMBO Journal (2004) 23, 2963 - 2971
  • doi:10.1038/sj.emboj.7600327

Published online: 22 July 2004

Structure of the bifunctional and Golgi-associated formiminotransferase cyclodeaminase octamer

Yuxin Mao1,ab, Nand K Vyas2,a, Meenakshi N Vyas1, Dong-Hua Chen2,3, Steven J Ludtke2,3, Wah Chiu2,3 and Florante A Quiocho1,2

  1. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, USA
  2. Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA
  3. National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, TX, USA

Correspondence to:

Florante A Quiocho, Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Tel.: +1 713 798 6565; Fax: +1 713 798 8516; E-mail: faq@bcm.tmc.edu

aThese authors contributed equally to this work

bPresent address: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA

Received 10 May 2004; Accepted 21 June 2004

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.

  • Keywords:

    • hepatitis autoantigen,
    • intermediate channeling,
    • protein assembly,
    • structure,
    • vimentin
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