An aspartyl protease directs malaria effector proteins to the host cell.

Nature
Justin A BoddeyAlan F Cowman

Abstract

Plasmodium falciparum causes the virulent form of malaria and disease manifestations are linked to growth inside infected erythrocytes. To survive and evade host responses the parasite remodels the erythrocyte by exporting several hundred effector proteins beyond the surrounding parasitophorous vacuole membrane. A feature of exported proteins is a pentameric motif (RxLxE/Q/D) that is a substrate for an unknown protease. Here we show that the protein responsible for cleavage of this motif is plasmepsin V (PMV), an aspartic acid protease located in the endoplasmic reticulum. PMV cleavage reveals the export signal (xE/Q/D) at the amino terminus of cargo proteins. Expression of an identical mature protein with xQ at the N terminus generated by signal peptidase was not exported, demonstrating that PMV activity is essential and linked with other key export events. Identification of the protease responsible for export into erythrocytes provides a novel target for therapeutic intervention against this devastating disease.

References

Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C Raventos-SuarezR L Nagel
Jun 24, 1994·Science·L H MillerG Milon
Feb 14, 2002·International Journal for Parasitology·Manoj T DuraisinghAlan F Cowman
Aug 2, 2003·Science·Karine G Le RochElizabeth A Winzeler
Jun 30, 2004·Journal of Molecular Biology·Jannick Dyrløv BendtsenSøren Brunak
Dec 14, 2004·Science·Matthias MartiAlan F Cowman
Feb 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Markus MeissnerBrendan S Crabb
Jun 14, 2005·Molecular and Biochemical Parasitology·Ellen KnuepferAlan F Cowman
Jun 18, 2005·The EMBO Journal·Jude M PrzyborskiMichael Lanzer
Jul 19, 2005·Molecular and Biochemical Parasitology·Michael Klemba, Daniel E Goldberg
Mar 2, 2006·Genome Biology·Tobias J SargeantAlan F Cowman
Jun 7, 2008·Molecular and Biochemical Parasitology·Henry H ChangMichael A Marletta
Jun 14, 2008·PLoS Pathogens·Christiaan van OoijKasturi Haldar
Oct 10, 2008·Nature·Jane M CarltonClaire M Fraser-Liggett
Apr 17, 2009·Nature Reviews. Microbiology·Alexander G MaierLeann Tilley
Jun 19, 2009·Nature·Tania F de Koning-WardBrendan S Crabb

❮ Previous
Next ❯

Citations

Feb 22, 2012·Cell Host & Microbe·Rays H Y Jiang, Matthias Marti
Oct 1, 2013·Molecular and Biochemical Parasitology·Joachim M MatzTaco W A Kooij
Apr 26, 2011·Journal of the American Chemical Society·Zhengrong WeiTahei Tahara
Jul 5, 2013·The Journal of Physical Chemistry. a·Aaron W HarrisonDaniel M Neumark
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Stephan WawraPieter van West
Mar 25, 2010·Molecular & Cellular Proteomics : MCP·Francesco SilvestriniPietro Alano
Mar 30, 2013·The Journal of Infectious Diseases·Charlotte V HobbsPatrick E Duffy
Nov 4, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·William J CookDebasish Chattopadhyay
Aug 31, 2011·Antimicrobial Agents and Chemotherapy·Christian Nsanzabana, Philip J Rosenthal
Sep 13, 2011·Eukaryotic Cell·Geoffrey K Kilili, Douglas J LaCount
Jul 3, 2013·Annual Review of Microbiology·Justin A Boddey, Alan F Cowman
Jun 17, 2011·BMC Evolutionary Biology·Christian PickThorsten Burmester
May 24, 2011·BMC Genomics·John KayJan A L van Kan
Mar 6, 2012·BMC Genomics·Timothy G LilburnYufeng Wang
May 28, 2013·International Journal of Cell Biology·Jasmin LindnerCarsten Wrenger
Apr 22, 2014·Proceedings of the National Academy of Sciences of the United States of America·Daniel FloreaHans M Wyss
Nov 29, 2013·Proceedings of the National Academy of Sciences of the United States of America·Esther Mundwiler-Pachlatko, Hans-Peter Beck
Feb 2, 2011·Expert Opinion on Therapeutic Targets·Serena TschanJürgen F J Kun
Mar 1, 2016·Frontiers in Microbiology·Rani SoniTarun K Bhatt
Sep 4, 2015·Nature Structural & Molecular Biology·Daniel E Goldberg
Jul 28, 2015·Nature Structural & Molecular Biology·Anthony N HodderAlan F Cowman
Jul 5, 2016·Nature Reviews. Microbiology·Tania F de Koning-WardPaul R Gilson
Nov 9, 2016·Scientific Reports·Manuel RhielJude M Przyborski
May 29, 2012·Anais Da Academia Brasileira De Ciências·Laura N CruzCélia R S Garcia
Feb 14, 2017·International Journal for Parasitology·Babu S MastanSatish Mishra
Apr 6, 2017·Parasitology International·Leandro Stefano SangenitoMarta H Branquinha
Dec 23, 2016·PLoS Pathogens·Antonio CassoneBernhard Hube

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
transfection
FRET
acetylation

Software Mentioned

extract
msn
PEXEL
MASCOT
GraphPad Prism
Axiovision

Related Concepts

Related Feeds

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.