Membrane association of monotopic phosphoglycosyl transferase underpins function

Membrane association of monotopic phosphoglycosyl transferase underpins function


Play all audios:


ABSTRACT Polyprenol phosphate phosphoglycosyl transferases (PGTs) catalyze the first membrane-committed step in assembly of essential glycoconjugates. Currently there is no


structure–function information to describe how monotopic PGTs coordinate the reaction between membrane-embedded and soluble substrates. We describe the structure and mode of membrane


association of PglC, a PGT from _Campylobacter concisus_. The structure reveals a unique architecture, provides mechanistic insight and identifies ligand-binding determinants for PglC and


the monotopic PGT superfamily. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your


institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $29.99 / 30 days cancel any time Learn more Subscribe to this journal


Receive 12 print issues and online access $259.00 per year only $21.58 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices


may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support


SIMILAR CONTENT BEING VIEWED BY OTHERS PEPTIDOGLYCAN BIOSYNTHESIS IS DRIVEN BY LIPID TRANSFER ALONG ENZYME-SUBSTRATE AFFINITY GRADIENTS Article Open access 27 April 2022 MOLECULAR BASIS OF


THE INOSITOL DEACYLASE PGAP1 INVOLVED IN QUALITY CONTROL OF GPI-AP BIOGENESIS Article Open access 02 January 2024 INSIGHT INTO THE DUAL FUNCTION OF LIPID PHOSPHATE PHOSPHATASE PGPB INVOLVED


IN TWO ESSENTIAL CELL-ENVELOPE METABOLIC PATHWAYS IN _ESCHERICHIA COLI_ Article Open access 06 August 2020 REFERENCES * Lukose, V., Walvoort, M. T. C. & Imperiali, B. _Glycobiology_ 27,


820–833 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Price, N. P. & Momany, F. A. _Glycobiology_ 15, 29R–42R (2005). Article  CAS  PubMed  Google Scholar  * Chung, B.


C. et al. _Science_ 341, 1012–1016 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Lukose, V. et al. _Biochemistry_ 54, 7326–7334 (2015). Article  CAS  PubMed  Google Scholar


  * Tytgat, H. L. & Lebeer, S. _Microbiol. Mol. Biol. Rev._ 78, 372–417 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Bugg, T. D., Rodolis, M. T., Mihalyi, A. &


Jamshidi, S. _Bioorg. Med. Chem._ 24, 6340–6347 (2016). Article  CAS  PubMed  Google Scholar  * Das, D., Kuzmic, P. & Imperiali, B. _Proc. Natl Acad. Sci. USA_ 114, 7019–7024 (2017).


Article  CAS  PubMed  PubMed Central  Google Scholar  * Al-Dabbagh, B. et al. _Biochimie._ 127, 249–257 (2016). Article  CAS  PubMed  Google Scholar  * Hartley, M. D., Schneggenburger, P. E.


& Imperiali, B. _Proc. Natl Acad. Sci. USA_ 110, 20863–20870 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Holm, L. & Rosenstrom, P. _Nucleic Acids Res._ 38,


W545–W549 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Aoki, S., Thomas, A., Decaffmeyer, M., Brasseur, R. & Epand, R. M. _J. Biol. Chem._ 285, 33371–33380 (2010).


Article  CAS  PubMed  PubMed Central  Google Scholar  * Heijne, G. _EMBO J._ 5, 3021–3027 (1986). Article  CAS  PubMed  PubMed Central  Google Scholar  * Furlong, S. E., Ford, A.,


Albarnez-Rodriguez, L. & Valvano, M. A. _Sci. Rep._ 5, 9178 (2015). Article  PubMed  PubMed Central  Google Scholar  * Patel, K. B., Ciepichal, E., Swiezewska, E. & Valvano, M. A.


_Glycobiology_ 22, 116–122 (2012). Article  CAS  PubMed  Google Scholar  * Nasie, I., Steiner-Mordoch, S. & Schuldiner, S. _Methods Mol. Biol._ 1033, 121–130 (2013). Article  CAS  PubMed


  Google Scholar  * Eisenberg, D., Schwarz, E., Komaromy, M. & Wall, R. _J. Mol. Biol._ 179, 125–142 (1984). Article  CAS  PubMed  Google Scholar  * Zidovetzki, R., Rost, B., Armstrong,


D. L. & Pecht, I. _Biophys. Chem._ 100, 555–575 (2003). Article  CAS  PubMed  Google Scholar  * Jones, S., Daley, D. T., Luscombe, N. M., Berman, H. M. & Thornton, J. M. _Nucleic


Acids Res._ 29, 943–954 (2001). Article  CAS  PubMed  PubMed Central  Google Scholar  * Lloyd, A. J., Brandish, P. E., Gilbey, A. M. & Bugg, T. D. H. _J. Bacteriol._ 186, 1747–1757


(2004). Article  CAS  PubMed  PubMed Central  Google Scholar  * Amer, A. O. & Valvano, M. A. _Microbiology_ 148, 571–582 (2002). Article  CAS  PubMed  Google Scholar  * Pace, C. N. &


Scholtz, J. M. _Biophys. J._ 75, 422–427 (1998). Article  CAS  PubMed  PubMed Central  Google Scholar  * Allen, K. N. & Dunaway-Mariano, D. _Curr. Opin. Struct. Biol._ 41, 172–179


(2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Ardiccioni, C. et al. _Nat. Commun._ 7, 10175 (2016). Article  CAS  PubMed  PubMed Central  Google Scholar  * Studier, F. W.


_Protein Expr. Purif._ 41, 207–234 (2005). Article  CAS  PubMed  Google Scholar  * Weeks, S. D., Drinker, M. & Loll, P. J. _Protein Expr. Purif._ 53, 40–50 (2007). Article  CAS  PubMed 


Google Scholar  * Koszelak-Rosenblum, M. et al. _Protein Sci._ 18, 1828–1839 (2009). Article  CAS  PubMed  PubMed Central  Google Scholar  * Adams, P. D. et al. _Acta Crystallogr. D Biol.


Crystallogr._ 66, 213–221 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Schneider, T. R. & Sheldrick, G. M. _Acta Crystallogr. D Biol. Crystallogr_ 58, 1772–1779


(2002). Article  CAS  PubMed  Google Scholar  * Terwilliger, T. C. & Acta Crystallogr., D. _Biol. Crystallogr._ 56, 965–972 (2000). Article  CAS  Google Scholar  * Wang, S., Sun, S., Li,


Z., Zhang, R. & Xu, J. _PLoS Comput. Biol._ 13, e1005324 (2017). Article  CAS  PubMed  PubMed Central  Google Scholar  * Ovchinnikov, S. et al. _Science_ 355, 294–298 (2017). Article 


CAS  PubMed  PubMed Central  Google Scholar  * McCoy, A. J. et al. _J. Appl. Crystallogr._ 40, 658–674 (2007). Article  CAS  PubMed  PubMed Central  Google Scholar  * Emsley, P., Lohkamp,


B., Scott, W. G. & Cowtan, K. _Acta. Crystallogr. D Biol. Crystallogr._ 66, 486–501 (2010). Article  CAS  PubMed  PubMed Central  Google Scholar  * Afonine, P. V. et al. _Acta.


Crystallogr. D Biol. Crystallogr._ 68, 352–367 (2012). Article  CAS  PubMed  PubMed Central  Google Scholar  * Baker, N. A., Sept, D., Joseph, S., Holst, M. J. & McCammon, J. A. _Proc.


Natl Acad. Sci. USA_ 98, 10037–10041 (2001). Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We thank K. Rajashankar for assistance with phasing


and the staff at NECAT (APS) for facilitating X-ray data collection. Financial support for this work was provided by the National Institutes of Health: R01-GM039334 to B.I., the Predoctoral


Training Program in the Biological Sciences (T32-GM007287) to S.E. and the Biomolecular Pharmacology Program Grant (T32-GM008541) to L.C.R. This work is also based upon research conducted at


the Northeastern Collaborative Access Team beamlines 24-ID-E and 24-ID-C, which is funded by the National Institute of General Medical Sciences from the National Institutes of Health (P41


GM103403). AUTHOR INFORMATION Author notes * These authors contributed equally: Leah C. Ray and Debasis Das. AUTHORS AND AFFILIATIONS * Program in Biomolecular Pharmacology, Boston


University School of Medicine, Boston, MA, USA Leah C. Ray & Karen N. Allen * Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA Debasis Das, Sonya Entova 


& Barbara Imperiali * Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA Debasis Das, Vinita Lukose & Barbara Imperiali * Department of Chemistry,


Boston University, Boston, MA, USA Andrew J. Lynch & Karen N. Allen Authors * Leah C. Ray View author publications You can also search for this author inPubMed Google Scholar * Debasis


Das View author publications You can also search for this author inPubMed Google Scholar * Sonya Entova View author publications You can also search for this author inPubMed Google Scholar *


Vinita Lukose View author publications You can also search for this author inPubMed Google Scholar * Andrew J. Lynch View author publications You can also search for this author inPubMed 


Google Scholar * Barbara Imperiali View author publications You can also search for this author inPubMed Google Scholar * Karen N. Allen View author publications You can also search for this


author inPubMed Google Scholar CONTRIBUTIONS L.C.R. crystallized, collected data, determined the structure, refined and analyzed the model of PglC and performed phosphate release kinetics;


D.D. optimized expression, designed and made constructs, expressed and purified PglC, carried out lipid analysis and analyzed the structure. S.E. designed and performed SCAM analyses. V.L.


designed and purified original constructs for crystallization and A.J.L. obtained the original crystallization conditions. L.C.R., D.D. and S.E. wrote the manuscript. B.I. and K.N.A.


conceived the project, designed experiments, assisted with data analysis and interpretation, and critically edited the manuscript. CORRESPONDING AUTHORS Correspondence to Barbara Imperiali


or Karen N. Allen. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE: Springer Nature remains neutral with regard to


jurisdictional claims in published maps and institutional affiliations. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–11 and Supplementary Tables 1–5


REPORTING SUMMARY DATASET 1 Supplementary Dataset 1 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ray, L.C., Das, D., Entova, S. _et al._ Membrane


association of monotopic phosphoglycosyl transferase underpins function. _Nat Chem Biol_ 14, 538–541 (2018). https://doi.org/10.1038/s41589-018-0054-z Download citation * Received: 07


November 2017 * Accepted: 14 March 2018 * Published: 16 May 2018 * Issue Date: June 2018 * DOI: https://doi.org/10.1038/s41589-018-0054-z SHARE THIS ARTICLE Anyone you share the following


link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature


SharedIt content-sharing initiative