부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.molbiopara.2008.04.011 Byline: Henry H. Chang (a), Arnold M. Falick (e), Peter M. Carlton (f), John W. Sedat (f), Joseph L. DeRisi (f)(g), Michael A. Marletta (a)(b)(c)(d) Keywords: Malaria; Plasmodium falciparum; Protein export; N-acetylation; Endoplasmic reticulum; Brefeldin A Abbreviations: BFA, brefeldin A; CID, collision-induced dissociation; ER, endoplasmic reticulum; GFP, green fluorescent protein; KAHRP, knob-associated histidine-rich protein; MALDI-TOF, matrix-assisted laser/desorption/ionization time-of-flight; MS, mass spectrometry; Nat, N-acetyltransferase; PEXEL, Plasmodium export element; PVM, parasitophorous vacuolar membrane; PV, parasitophorous vacuole; PfEMP1, P. falciparum erythrocyte membrane protein 1; PfEMP2, P. falciparum erythrocyte membrane protein 2; PfHRPII, P. falciparum histidine-rich protein II; RBC, red blood cell; RCC, red cell cytosol; RCM, red cell membrane; SPC, signal peptidase complex Abstract: Malaria parasites utilize a short N-terminal amino acid motif termed the Plasmodium export element (PEXEL) to export an array of proteins to the host erythrocyte during blood stage infection. Using immunoaffinity chromatography and mass spectrometry, insight into this signal-mediated trafficking mechanism was gained by discovering that the PEXEL motif is cleaved and N-acetylated. PfHRPII and PfEMP2 are two soluble proteins exported by Plasmodium falciparum that were demonstrated to undergo PEXEL cleavage and N-acetylation, thus indicating that this N-terminal processing may be general to many exported soluble proteins. It was established that PEXEL processing occurs upstream of the brefeldin A-sensitive trafficking step in the P. falciparum secretory pathway, therefore cleavage and N-acetylation of the PEXEL motif occurs in the endoplasmic reticulum (ER) of the parasite. Furthermore, it was shown that the recognition of the processed N-terminus of exported proteins within the parasitophorous vacuole may be crucial for protein transport to the host erythrocyte. It appears that the PEXEL may be defined as a novel ER peptidase cleavage site and a classical N-acetyltransferase substrate sequence. Author Affiliation: (a) Department of Chemistry, University of California, Berkeley, CA 94720, USA (b) Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA (c) Division of Physical Biosciences, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA (d) QB3 Institute, University of California, Berkeley, 570 Stanley Hall, Berkeley, CA 94720-3220, USA (e) Howard Hughes Medical Institute Mass Spectrometry Laboratory, University of California, Berkeley, CA 94720, USA (f) Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA (g) Howard Hughes Medical Institute, USA Article History: Received 7 December 2007; Revised 18 April 2008; Accepted 22 April 2008