Arabidopsis thaliana serine hydroxymethyltransferases: functions, structures, and perspectives

Isabel Nogués; Bartosz Sekula; Sebastiana Angelaccio; Marta Grzechowiak; Angela Tramonti; Roberto Contestabile; Milosz Ruszkowski

doi:10.1016/j.plaphy.2022.07.025

Arabidopsis thaliana serine hydroxymethyltransferases: functions, structures, and perspectives

Plant Physiol Biochem. 2022 Sep 15:187:37-49. doi: 10.1016/j.plaphy.2022.07.025. Epub 2022 Jul 31.

Authors

Isabel Nogués¹, Bartosz Sekula², Sebastiana Angelaccio³, Marta Grzechowiak⁴, Angela Tramonti⁵, Roberto Contestabile³, Milosz Ruszkowski⁶

Affiliations

¹ Research Institute on Terrestrial Ecosystems, Italian National Research Council, Monterotondo Scalo, Rome, Italy.
² Synchrotron Radiation Research Section of MCL, National Cancer Institute, Argonne, IL, USA; Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Lodz, Poland.
³ Department of Biochemical Sciences "A. Rossi Fanelli", Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, P.le Aldo Moro 5, 00185, Rome, Italy.
⁴ Department of Structural Biology of Eukaryotes, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
⁵ Institute of Molecular Biology and Pathology, National Research Council, Rome, Italy.
⁶ Synchrotron Radiation Research Section of MCL, National Cancer Institute, Argonne, IL, USA; Department of Structural Biology of Eukaryotes, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland. Electronic address: mruszkowski@ibch.poznan.pl.

PMID: 35947902
DOI: 10.1016/j.plaphy.2022.07.025

Abstract

Serine hydroxymethyltransferase (SHM) is one of the hallmarks of one-carbon metabolism. In plants, isoforms of SHM participate in photorespiration and/or transfer the one-carbon unit from L-serine to tetrahydrofolate (THF), hence producing 5,10-CH₂-THF that is needed, e.g., for biosynthesis of methionine, thymidylate, and purines. These links highlight the importance of SHM activity in DNA biogenesis, its epigenetic methylations, and in stress responses. Plant genomes encode several SHM isoforms that localize to cytosol, mitochondria, plastids, and nucleus. In this work, we present a thorough functional and structural characterization of all seven SHM isoforms from Arabidopsis thaliana (AtSHM1-7). In particular, we analyzed tissue-specific expression profiles of the AtSHM genes. We also compared catalytic properties of the active AtSHM1-4 in terms of catalytic efficiency in both directions and inhibition by the THF substrate. Despite numerous attempts to rescue the SHM activity of AtSHM5-7, we failed, which points towards different physiological functions of these isoforms. Comparative analysis of experimental and predicted three-dimensional structures of AtSHM1-7 proteins indicated differences in regions that surround the entrance to the active site cavity.