AftD Functions As an α1 → 5 Arabinofuranosyltransferase Involved in the Biosynthesis of the Mycobacterial Cell Wall Core

Overview

Journal Cell Surf

Publisher Elsevier

Date 2018 Jul 13

PMID 29998212

Citations 11

Authors

Luke J Alderwick

Helen L Birch

Karin Krumbach

Michael Bott

Lothar Eggeling

Gurdyal S Besra

Affiliations

Soon will be listed here.

Abstract

Arabinogalactan (AG) is an essential structural macromolecule present in the cell wall of , serving to connect peptidoglycan with the outer mycolic acid layer. The D-arabinan segment is a highly branched component of AG and is assembled in a step-wise fashion by a variety of arabinofuranosyltransferases (AraT). We have previously used as a model organism to study these complex processes which are otherwise essential in mycobacteria. In order to further our understanding of the molecular basis of AG assembly, we investigated the role of a fourth AraT, now termed AftD by generating single (Δ) and double deletion (Δ Δ) mutants of . We demonstrate that AftD functions as an α(1 → 5) AraT and reveal the point at which it exerts its activity in the AG biosynthetic pathway.

Citing Articles

The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth.

Franklin A, Salgueiro V, Layton A, Sullivan R, Mize T, Vazquez-Iniesta L Nat Commun. 2024; 15(1):5740.

PMID: 38982040 PMC: 11233589. DOI: 10.1038/s41467-024-50051-3.

The conserved σD envelope stress response monitors multiple aspects of envelope integrity in corynebacteria.

Hart E, Lyerly E, Bernhardt T PLoS Genet. 2024; 20(6):e1011127.

PMID: 38829907 PMC: 11175481. DOI: 10.1371/journal.pgen.1011127.

The mycobacterial glycoside hydrolase LamH enables capsular arabinomannan release and stimulates growth.

Franklin A, Layton A, Mize T, Salgueiro V, Sullivan R, Benedict S bioRxiv. 2023; .

PMID: 37961452 PMC: 10634837. DOI: 10.1101/2023.10.26.563968.

Structure and Function of Mycobacterial Arabinofuranosyltransferases.

Tan Y, Mancia F Subcell Biochem. 2022; 99:379-391.

PMID: 36151383 DOI: 10.1007/978-3-031-00793-4_12.

MmpA, a Conserved Membrane Protein Required for Efficient Surface Transport of Trehalose Lipids in Corynebacterineae.

Cashmore T, Klatt S, Brammananth R, Rainczuk A, Crellin P, McConville M Biomolecules. 2021; 11(12).

PMID: 34944401 PMC: 8698533. DOI: 10.3390/biom11121760.

References

Birch H, Alderwick L, Bhatt A, Rittmann D, Krumbach K, Singh A . Biosynthesis of mycobacterial arabinogalactan: identification of a novel alpha(1-->3) arabinofuranosyltransferase. Mol Microbiol. 2008; 69(5):1191-206. PMC: 2610374. DOI: 10.1111/j.1365-2958.2008.06354.x. View

Schafer A, Tauch A, Jager W, Kalinowski J, Thierbach G, Puhler A . Small mobilizable multi-purpose cloning vectors derived from the Escherichia coli plasmids pK18 and pK19: selection of defined deletions in the chromosome of Corynebacterium glutamicum. Gene. 1994; 145(1):69-73. DOI: 10.1016/0378-1119(94)90324-7. View

McNeil M, Daffe M, Brennan P . Location of the mycolyl ester substituents in the cell walls of mycobacteria. J Biol Chem. 1991; 266(20):13217-23. View

Abbott D, Hrynuik S, Boraston A . Identification and characterization of a novel periplasmic polygalacturonic acid binding protein from Yersinia enterolitica. J Mol Biol. 2007; 367(4):1023-33. DOI: 10.1016/j.jmb.2007.01.030. View

Wesener D, Levengood M, Kiessling L . Comparing Galactan Biosynthesis in and . J Biol Chem. 2017; 292(7):2944-2955. PMC: 5314189. DOI: 10.1074/jbc.M116.759340. View

Bhowruth V, Alderwick L, Brown A, Bhatt A, Besra G . Tuberculosis: a balanced diet of lipids and carbohydrates. Biochem Soc Trans. 2008; 36(Pt 4):555-65. DOI: 10.1042/BST0360555. View

Lee R, Brennan P, Besra G . Mycobacterial arabinan biosynthesis: the use of synthetic arabinoside acceptors in the development of an arabinosyl transfer assay. Glycobiology. 1998; 7(8):1121-8. DOI: 10.1093/glycob/7.8.1121. View

Sonnhammer E, von Heijne G, KROGH A . A hidden Markov model for predicting transmembrane helices in protein sequences. Proc Int Conf Intell Syst Mol Biol. 1998; 6:175-82. View

Seidel M, Alderwick L, Birch H, Sahm H, Eggeling L, Besra G . Identification of a novel arabinofuranosyltransferase AftB involved in a terminal step of cell wall arabinan biosynthesis in Corynebacterianeae, such as Corynebacterium glutamicum and Mycobacterium tuberculosis. J Biol Chem. 2007; 282(20):14729-40. DOI: 10.1074/jbc.M700271200. View

10.

Telenti A, Philipp W, Sreevatsan S, Bernasconi C, Stockbauer K, Wieles B . The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol. Nat Med. 1997; 3(5):567-70. DOI: 10.1038/nm0597-567. View

11.

Jankute M, Byng C, Alderwick L, Besra G . Elucidation of a protein-protein interaction network involved in Corynebacterium glutamicum cell wall biosynthesis as determined by bacterial two-hybrid analysis. Glycoconj J. 2014; 31(6-7):475-83. PMC: 4213368. DOI: 10.1007/s10719-014-9549-3. View

12.

Alderwick L, Seidel M, Sahm H, Besra G, Eggeling L . Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis. J Biol Chem. 2006; 281(23):15653-61. DOI: 10.1074/jbc.M600045200. View

13.

Lee R, Li W, Chatterjee D, Lee R . Rapid structural characterization of the arabinogalactan and lipoarabinomannan in live mycobacterial cells using 2D and 3D HR-MAS NMR: structural changes in the arabinan due to ethambutol treatment and gene mutation are observed. Glycobiology. 2004; 15(2):139-51. DOI: 10.1093/glycob/cwh150. View

14.

Alderwick L, Dover L, Seidel M, Gande R, Sahm H, Eggeling L . Arabinan-deficient mutants of Corynebacterium glutamicum and the consequent flux in decaprenylmonophosphoryl-D-arabinose metabolism. Glycobiology. 2006; 16(11):1073-81. DOI: 10.1093/glycob/cwl030. View

15.

Alderwick L, Radmacher E, Seidel M, Gande R, Hitchen P, Morris H . Deletion of Cg-emb in corynebacterianeae leads to a novel truncated cell wall arabinogalactan, whereas inactivation of Cg-ubiA results in an arabinan-deficient mutant with a cell wall galactan core. J Biol Chem. 2005; 280(37):32362-71. DOI: 10.1074/jbc.M506339200. View

16.

Besra G, Khoo K, McNeil M, Dell A, Morris H, Brennan P . A new interpretation of the structure of the mycolyl-arabinogalactan complex of Mycobacterium tuberculosis as revealed through characterization of oligoglycosylalditol fragments by fast-atom bombardment mass spectrometry and 1H nuclear magnetic.... Biochemistry. 1995; 34(13):4257-66. DOI: 10.1021/bi00013a015. View

17.

Liu J, Mushegian A . Three monophyletic superfamilies account for the majority of the known glycosyltransferases. Protein Sci. 2003; 12(7):1418-31. PMC: 2323934. DOI: 10.1110/ps.0302103. View

18.

Seidel M, Alderwick L, Sahm H, Besra G, Eggeling L . Topology and mutational analysis of the single Emb arabinofuranosyltransferase of Corynebacterium glutamicum as a model of Emb proteins of Mycobacterium tuberculosis. Glycobiology. 2006; 17(2):210-9. DOI: 10.1093/glycob/cwl066. View

19.

Uitdehaag J, Kalk K, van der Veen B, Dijkhuizen L, Dijkstra B . The cyclization mechanism of cyclodextrin glycosyltransferase (CGTase) as revealed by a gamma-cyclodextrin-CGTase complex at 1.8-A resolution. J Biol Chem. 1999; 274(49):34868-76. DOI: 10.1074/jbc.274.49.34868. View

20.

Abrahams K, Besra G . Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target. Parasitology. 2016; 145(2):116-133. PMC: 5964476. DOI: 10.1017/S0031182016002377. View

AftD Functions As an α1 → 5 Arabinofuranosyltransferase Involved in the Biosynthesis of the Mycobacterial Cell Wall Core

AftD Functions As an α1 → 5 Arabinofuranosyltransferase Involved in the Biosynthesis of the Mycobacterial Cell Wall Core