title: Structure determination of human Fas apoptosis inhibitory molecule and identification of the critical residues linking the interdomain interaction to the anti-apoptotic activity.
abstract: Fas apoptosis inhibitory molecule (FAIM) is a highly conserved anti-apoptotic protein which plays important roles in cells. There are two isoforms of FAIM, of which the short isoform FAIM-S is broadly expressed in all tissues, whereas the long isoform FAIM-L is exclusively expressed in the nervous system. No structure of human FAIM has been reported to date and the detailed molecular mechanisms underlying the anti-apoptotic function of FAIM remain unknown. Here, the crystal structure of the human FAIM-S N-terminal domain (NTD) and the NMR solution structure of the human FAIM-S C-terminal domain (CTD) were determined. The structures revealed that the NTD and CTD adopt a similar protein fold containing eight antiparallel β-strands which form two sheets. Both structural and biochemical analyses implied that the NTD exists as a dimer and the CTD as a monomer and that they can interact with each other. Several critical residues were identified to be involved in this interaction. Moreover, mutations of these critical residues also interfered in the anti-apoptotic activity of FAIM-S. Thus, the structural and functional data presented here will provide insight into the anti-apoptotic mechanism of FAIM-S.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Guoming
authors.initials: G
authors.lastname: Li
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Linglong
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Shuaipeng
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Changwen
authors.initials: C
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, Peking University, Beijing 100871, People's Republic of China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D003460:Crystallization; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D019014:fas Receptor / Q000737:chemistry*
chemical_list: D019014:fas Receptor
keywords: Fas apoptosis inhibitory molecule; anti-apoptotic protein; interdomain interaction