Structural basis of HypK regulating N-terminal acetylation by the NatA complex

• Published in: Nature communications Vol. 8; no. 1; p. 15726
• Main Authors: Weyer, Felix Alexander, Gumiero, Andrea, Lapouge, Karine, Bange, Gert, Kopp, Jürgen, Sinning, Irmgard
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 06.06.2017; Nature Portfolio
• Subjects: Acetylation; Acetyltransferases - genetics; Apoptosis; Carrier Proteins - chemistry; Catalytic Domain; Cell cycle; Chaetomium; Crystal structure; Crystallography, X-Ray; Humans; Light; Models, Molecular; N-Terminal Acetyltransferase A - chemistry; Peptides - chemistry; Protein Binding; Protein Biosynthesis; Protein Denaturation; Protein Domains; Protein Multimerization; Protein Processing, Post-Translational; Protein Structure, Secondary; Proteins; Ribonucleic acid; RNA; Scattering, Radiation; Selenomethionine - chemistry; Yeast; Germany
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms15726

In eukaryotes, N-terminal acetylation is one of the most common protein modifications involved in a wide range of biological processes. Most N-acetyltransferase complexes (NATs) act co-translationally, with the heterodimeric NatA complex modifying the majority of substrate proteins. Here we show that the Huntingtin yeast two-hybrid protein K (HypK) binds tightly to the NatA complex comprising the auxiliary subunit Naa15 and the catalytic subunit Naa10. The crystal structures of NatA bound to HypK or to a N-terminal deletion variant of HypK were determined without or with a bi-substrate analogue, respectively. The HypK C-terminal region is responsible for high-affinity interaction with the C-terminal part of Naa15. In combination with acetylation assays, the HypK N-terminal region is identified as a negative regulator of the NatA acetylation activity. Our study provides mechanistic insights into the regulation of this pivotal protein modification.