TerC Proteins Function During Protein Secretion to Metalate Exoenzymes

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Oct 4

PMID 37794032

Authors

Bixi He

Ankita J Sachla

John D Helmann

Affiliations

Soon will be listed here.

Abstract

Cytosolic metalloenzymes acquire metals from buffered intracellular pools. How exported metalloenzymes are appropriately metalated is less clear. We provide evidence that TerC family proteins function in metalation of enzymes during export through the general secretion (Sec-dependent) pathway. Bacillus subtilis strains lacking MeeF(YceF) and MeeY(YkoY) have a reduced capacity for protein export and a greatly reduced level of manganese (Mn) in the secreted proteome. MeeF and MeeY copurify with proteins of the general secretory pathway, and in their absence the FtsH membrane protease is essential for viability. MeeF and MeeY are also required for efficient function of the Mn-dependent lipoteichoic acid synthase (LtaS), a membrane-localized enzyme with an extracytoplasmic active site. Thus, MeeF and MeeY, representative of the widely conserved TerC family of membrane transporters, function in the co-translocational metalation of Mn-dependent membrane and extracellular enzymes.

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References

Errington J, van der Aart L . Microbe Profile: : model organism for cellular development, and industrial workhorse. Microbiology (Reading). 2020; 166(5):425-427. PMC: 7376258. DOI: 10.1099/mic.0.000922. View

Schulze R, Komar J, Botte M, Allen W, Whitehouse S, Gold V . Membrane protein insertion and proton-motive-force-dependent secretion through the bacterial holo-translocon SecYEG-SecDF-YajC-YidC. Proc Natl Acad Sci U S A. 2014; 111(13):4844-9. PMC: 3977283. DOI: 10.1073/pnas.1315901111. View

Percy M, Grundling A . Lipoteichoic acid synthesis and function in gram-positive bacteria. Annu Rev Microbiol. 2014; 68:81-100. DOI: 10.1146/annurev-micro-091213-112949. View

Kunkle D, Skaar E . Moving metals: How microbes deliver metal cofactors to metalloproteins. Mol Microbiol. 2023; 120(4):547-554. PMC: 10592388. DOI: 10.1111/mmi.15117. View

Thines L, Deschamps A, Sengottaiyan P, Savel O, Stribny J, Morsomme P . The yeast protein Gdt1p transports Mn ions and thereby regulates manganese homeostasis in the Golgi. J Biol Chem. 2018; 293(21):8048-8055. PMC: 5971465. DOI: 10.1074/jbc.RA118.002324. View

Schneider A, Steinberger I, Strissel H, Kunz H, Manavski N, Meurer J . The Arabidopsis Tellurite resistance C protein together with ALB3 is involved in photosystem II protein synthesis. Plant J. 2014; 78(2):344-56. DOI: 10.1111/tpj.12474. View

Wormann M, Corrigan R, Simpson P, Matthews S, Grundling A . Enzymatic activities and functional interdependencies of Bacillus subtilis lipoteichoic acid synthesis enzymes. Mol Microbiol. 2011; 79(3):566-83. PMC: 3089822. DOI: 10.1111/j.1365-2958.2010.07472.x. View

Mason S, Vornhagen J, Smith S, Mike L, Mobley H, Bachman M . The Klebsiella pneumoniae Operon Enhances Stress Tolerance. Infect Immun. 2023; 91(2):e0055922. PMC: 9933665. DOI: 10.1128/iai.00559-22. View

Stewart L, Thaqi D, Kobe B, McEwan A, Waldron K, Djoko K . Handling of nutrient copper in the bacterial envelope. Metallomics. 2018; 11(1):50-63. DOI: 10.1039/c8mt00218e. View

10.

Potelle S, Morelle W, Dulary E, Duvet S, Vicogne D, Spriet C . Glycosylation abnormalities in Gdt1p/TMEM165 deficient cells result from a defect in Golgi manganese homeostasis. Hum Mol Genet. 2016; 25(8):1489-500. DOI: 10.1093/hmg/ddw026. View

11.

Waldron K, Robinson N . How do bacterial cells ensure that metalloproteins get the correct metal?. Nat Rev Microbiol. 2008; 7(1):25-35. DOI: 10.1038/nrmicro2057. View

12.

Thomas 3rd K, Rice C . Equilibrium binding behavior of magnesium to wall teichoic acid. Biochim Biophys Acta. 2015; 1848(10 Pt A):1981-7. PMC: 4554814. DOI: 10.1016/j.bbamem.2015.05.003. View

13.

Kwon K, Cho M . Deletion of the chloroplast-localized AtTerC gene product in Arabidopsis thaliana leads to loss of the thylakoid membrane and to seedling lethality. Plant J. 2008; 55(3):428-42. DOI: 10.1111/j.1365-313X.2008.03523.x. View

14.

Demaegd D, Foulquier F, Colinet A, Gremillon L, Legrand D, Mariot P . Newly characterized Golgi-localized family of proteins is involved in calcium and pH homeostasis in yeast and human cells. Proc Natl Acad Sci U S A. 2013; 110(17):6859-64. PMC: 3637739. DOI: 10.1073/pnas.1219871110. View

15.

Tjalsma H, Antelmann H, Jongbloed J, Braun P, Darmon E, Dorenbos R . Proteomics of protein secretion by Bacillus subtilis: separating the "secrets" of the secretome. Microbiol Mol Biol Rev. 2004; 68(2):207-33. PMC: 419921. DOI: 10.1128/MMBR.68.2.207-233.2004. View

16.

Pasquina L, Santa Maria J, Walker S . Teichoic acid biosynthesis as an antibiotic target. Curr Opin Microbiol. 2013; 16(5):531-7. PMC: 3834221. DOI: 10.1016/j.mib.2013.06.014. View

17.

Sharma R, Mishanina T . A riboswitch-controlled TerC family transporter Alx tunes intracellular manganese concentration in at alkaline pH. J Bacteriol. 2024; 206(7):e0016824. PMC: 11270866. DOI: 10.1128/jb.00168-24. View

18.

Hyyrylainen H, Vitikainen M, Thwaite J, Wu H, Sarvas M, Harwood C . D-Alanine substitution of teichoic acids as a modulator of protein folding and stability at the cytoplasmic membrane/cell wall interface of Bacillus subtilis. J Biol Chem. 2000; 275(35):26696-703. DOI: 10.1074/jbc.M003804200. View

19.

Chandrangsu P, Huang X, Gaballa A, Helmann J . Bacillus subtilis FolE is sustained by the ZagA zinc metallochaperone and the alarmone ZTP under conditions of zinc deficiency. Mol Microbiol. 2019; 112(3):751-765. PMC: 6736736. DOI: 10.1111/mmi.14314. View

20.

Thines L, Deschamps A, Stribny J, Morsomme P . Yeast as a Tool for Deeper Understanding of Human Manganese-Related Diseases. Genes (Basel). 2019; 10(7). PMC: 6678438. DOI: 10.3390/genes10070545. View