Home > Publications Database > Non-canonical Shedding of TNFα by SPPL2a Is Determined by the Conformational Flexibility of Its Transmembrane Helix. > print

001     154229
005     20240223115101.0
024 7 _ |a 10.1016/j.isci.2020.101775
|2 doi
024 7 _ |a pmid:33294784
|2 pmid
024 7 _ |a pmc:PMC7689174
|2 pmc
037 _ _ |a DZNE-2021-00090
041 _ _ |a English
082 _ _ |a 050
100 1 _ |a Spitz, Charlotte
|0 P:(DE-HGF)0
|b 0
245 _ _ |a Non-canonical Shedding of TNFα by SPPL2a Is Determined by the Conformational Flexibility of Its Transmembrane Helix.
260 _ _ |a St. Louis
|c 2020
|b Elsevier
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1708605238_31175
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Ectodomain (EC) shedding defines the proteolytic removal of a membrane protein EC and acts as an important molecular switch in signaling and other cellular processes. Using tumor necrosis factor (TNF)α as a model substrate, we identify a non-canonical shedding activity of SPPL2a, an intramembrane cleaving aspartyl protease of the GxGD type. Proline insertions in the TNFα transmembrane (TM) helix strongly increased SPPL2a non-canonical shedding, while leucine mutations decreased this cleavage. Using biophysical and structural analysis, as well as molecular dynamic simulations, we identified a flexible region in the center of the TNFα wildtype TM domain, which plays an important role in the processing of TNFα by SPPL2a. This study combines molecular biology, biochemistry, and biophysics to provide insights into the dynamic architecture of a substrate's TM helix and its impact on non-canonical shedding. Thus, these data will provide the basis to identify further physiological substrates of non-canonical shedding in the future.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
|0 G:(DE-HGF)POF3-342
|c POF3-342
|f POF III
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Biochemistry
|2 Other
650 _ 7 |a Biophysics
|2 Other
650 _ 7 |a Structural Biology
|2 Other
700 1 _ |a Schlosser, Christine
|0 P:(DE-2719)2812339
|b 1
|u dzne
700 1 _ |a Guschtschin-Schmidt, Nadja
|0 P:(DE-HGF)0
|b 2
700 1 _ |a Stelzer, Walter
|0 P:(DE-HGF)0
|b 3
700 1 _ |a Menig, Simon
|0 P:(DE-HGF)0
|b 4
700 1 _ |a Götz, Alexander
|0 P:(DE-HGF)0
|b 5
700 1 _ |a Haug-Kröper, Martina
|0 P:(DE-HGF)0
|b 6
700 1 _ |a Scharnagl, Christina
|0 P:(DE-HGF)0
|b 7
700 1 _ |a Langosch, Dieter
|0 P:(DE-2719)9001125
|b 8
|u dzne
700 1 _ |a Muhle-Goll, Claudia
|0 P:(DE-HGF)0
|b 9
700 1 _ |a Fluhrer, Regina
|0 P:(DE-2719)2000007
|b 10
|e Last author
773 _ _ |a 10.1016/j.isci.2020.101775
|g Vol. 23, no. 12, p. 101775 -
|0 PERI:(DE-600)2927064-9
|n 12
|p 101775
|t iScience
|v 23
|y 2020
|x 2589-0042
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/154229/files/DZNE-2021-00090.pdf
856 4 _ |y OpenAccess
|x pdfa
|u https://pub.dzne.de/record/154229/files/DZNE-2021-00090.pdf?subformat=pdfa
909 C O |o oai:pub.dzne.de:154229
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 1
|6 P:(DE-2719)2812339
910 1 _ |a External Institute
|0 I:(DE-HGF)0
|k Extern
|b 8
|6 P:(DE-2719)9001125
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 10
|6 P:(DE-2719)2000007
913 1 _ |a DE-HGF
|b Gesundheit
|l Erkrankungen des Nervensystems
|1 G:(DE-HGF)POF3-340
|0 G:(DE-HGF)POF3-342
|3 G:(DE-HGF)POF3
|2 G:(DE-HGF)POF3-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms and Model Systems
|x 0
913 2 _ |a DE-HGF
|b Programmungebundene Forschung
|l ohne Programm
|1 G:(DE-HGF)POF4-890
|0 G:(DE-HGF)POF4-899
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-800
|4 G:(DE-HGF)POF
|v ohne Topic
|x 0
914 1 _ |y 2020
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2022-11-16
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2022-11-16
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2022-11-16
915 _ _ |a Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
|0 LIC:(DE-HGF)CCBYNCND4
|2 HGFVOC
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b ISCIENCE : 2021
|d 2022-11-16
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2021-06-28T09:42:31Z
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2020-08-31
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2021-06-28T09:42:31Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2022-11-16
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2022-11-16
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Blind peer review
|d 2021-06-28T09:42:31Z
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2020-08-31
915 _ _ |a IF >= 5
|0 StatID:(DE-HGF)9905
|2 StatID
|b ISCIENCE : 2021
|d 2022-11-16
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2020-08-31
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2020-08-31
920 1 _ |0 I:(DE-2719)1110000-2
|k AG Fluhrer
|l Signal Peptide Peptidases as Models for γ-Secretase
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)1110000-2
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21