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Voss, M.* ; Fukumori, A.* ; Kuhn, P.H.* ; Künzel, U.* ; Klier, B.* ; Grammer, G.* ; Haug-Kröper, M.* ; Kremmer, E. ; Lichtenthaler, S.F.* ; Steiner, H.* ; Schröder, B.* ; Haass, C.* ; Fluhrer, R.*

Foamy virus envelope protein is a substrate for Signal Peptide Peptidase-Like 3 (SPPL3).

J. Biol. Chem. 287, 43401-43409 (2012)
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Signal peptide peptidase (SPP), its homologs, the SPP-like proteases SPPL2a/b/c and SPPL3, as well as presenilin, the catalytic subunit of the γ-secretase complex, are intramembrane-cleaving aspartyl proteases of the GxGD type. In this study, we identified the 18-kDa leader peptide (LP18) of the foamy virus envelope protein (FVenv) as a new substrate for intramembrane proteolysis by human SPPL3 and SPPL2a/b. In contrast to SPPL2a/b and γ-secretase, which require substrates with an ectodomain shorter than 60 amino acids for efficient intramembrane proteolysis, SPPL3 cleaves mutant FVenv lacking the proprotein convertase cleavage site necessary for the prior shedding. Moreover, the cleavage product of FVenv generated by SPPL3 serves as a new substrate for consecutive intramembrane cleavage by SPPL2a/b. Thus, human SPPL3 is the first GxGD-type aspartyl protease shown to be capable of acting like a sheddase, similar to members of the rhomboid family, which belong to the class of intramembrane-cleaving serine proteases.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter REGULATED INTRAMEMBRANE PROTEOLYSIS; GAMMA-SECRETASE ACTIVITY; ENV LEADER PROTEIN; ASPARTIC PROTEASE; TNF-ALPHA; CLEAVAGE; PRESENILIN; GLYCOPROTEIN; DOMAIN; IDENTIFICATION
Sprache englisch
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Zeitschrift Journal of Biological Chemistry, The
Quellenangaben Band: 287, Heft: 52, Seiten: 43401-43409 Artikelnummer: , Supplement: ,
Verlag American Society for Biochemistry and Molecular Biology
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501793-001
PubMed ID 23132852
DOI 10.1074/jbc.M112.371369
WOS ID WOS:000312940800021
Scopus ID 84871601715
Erfassungsdatum 2012-12-31
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