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PFN2 and NAA80 cooperate to efficiently acetylate the N-terminus of actin
Authors:Rasmus Ree  Laura Kind  Anna Kaziales  Sylvia Varland  Minglu Dai  Klaus Richter  Adrian Drazic  Thomas Arnesen
Affiliation:1.Department of Biomedicine, University of Bergen, Bergen, Norway;2.Department of Chemistry, Technische Universität München, Garching, Germany;3.Department of Biological Sciences, University of Bergen, Bergen, Norway;4.Department of Surgery, Haukeland University Hospital, Bergen, Norway
Abstract:The actin cytoskeleton is of profound importance to cell shape, division, and intracellular force generation. Profilins bind to globular (G-)actin and regulate actin filament formation. Although profilins are well-established actin regulators, the distinct roles of the dominant profilin, profilin 1 (PFN1), versus the less abundant profilin 2 (PFN2) remain enigmatic. In this study, we use interaction proteomics to discover that PFN2 is an interaction partner of the actin N-terminal acetyltransferase NAA80, and further confirm this by analytical ultracentrifugation. Enzyme assays with NAA80 and different profilins demonstrate that PFN2 binding specifically increases the intrinsic catalytic activity of NAA80. NAA80 binds PFN2 through a proline-rich loop, deletion of which abrogates PFN2 binding. Small-angle X-ray scattering shows that NAA80, actin, and PFN2 form a ternary complex and that NAA80 has partly disordered regions in the N-terminus and the proline-rich loop, the latter of which is partly ordered upon PFN2 binding. Furthermore, binding of PFN2 to NAA80 via the proline-rich loop promotes binding between the globular domains of actin and NAA80, and thus acetylation of actin. However, the majority of cellular NAA80 is stably bound to PFN2 and not to actin, and we propose that this complex acetylates G-actin before it is incorporated into filaments. In conclusion, we reveal a functionally specific role of PFN2 as a stable interactor and regulator of the actin N-terminal acetyltransferase NAA80, and establish the modus operandi for NAA80-mediated actin N-terminal acetylation, a modification with a major impact on cytoskeletal dynamics.
Keywords:N-terminal acetyltransferases   NAT   cytoskeleton   acetylation   post-translational modification (PTM)   protein-protein interaction   actin   profilin   small-angle X-ray scattering (SAXS)
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