title: Molecular Basis of Substrate Specific Acetylation by N-Terminal Acetyltransferase NatB.
abstract: The NatB N-terminal acetyltransferase specifically acetylates the N-terminal group of substrate protein peptides starting with Met-Asp/Glu/Asn/Gln. How NatB recognizes and acetylates these substrates remains unknown. Here, we report crystal structures of a NatB holoenzyme from Candida albicans in the presence of its co-factor CoA and substrate peptides. The auxiliary subunit Naa25 of NatB forms a horseshoe-like deck to hold specifically its catalytic subunit Naa20. The first two amino acids Met and Asp of a substrate peptide mediate the major interactions with the active site in the Naa20 subunit. The hydrogen bonds between the substrate Asp and pocket residues of Naa20 are essential to determine the NatB substrate specificity. Moreover, a hydrogen bond between the amino group of the substrate Met and a carbonyl group in the Naa20 active site directly anchors the substrate toward acetyl-CoA. Together, these structures define a unique molecular mechanism of specific N-terminal acetylation acted by NatB.
authors.affiliation: State Key Laboratory for Cellular Stress Biology, Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiang'an, Xiamen 361102, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hong
authors.affiliation: State Key Laboratory for Cellular Stress Biology, Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiang'an, Xiamen 361102, China.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Cai
authors.affiliation: State Key Laboratory for Cellular Stress Biology, Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiang'an, Xiamen 361102, China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Cellular Stress Biology, Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiang'an, Xiamen 361102, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ding
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Cellular Stress Biology, Department of Biomedical Sciences, School of Life Sciences, Xiamen University, Xiang'an, Xiamen 361102, China. Electronic address: ahan@xmu.edu.cn.
authors.forename: Aidong
authors.initials: A
authors.lastname: Han
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D002176:Candida albicans / Q000737:chemistry / Q000201:enzymology*; D020134:Catalytic Domain; D006860:Hydrogen Bonding; D008958:Models, Molecular; D063210:N-Terminal Acetyltransferase B / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D013379:Substrate Specificity
chemical_list: D063210:N-Terminal Acetyltransferase B
keywords: N-terminal acetylation; N-terminal acetyltransferase; NatB; acetylation; crystal structure; protein post-translational modification