ArticleThe Journal of biological chemistry2012
The α-helical content of the transmembrane domain of the British dementia protein-2 (Bri2) determines its processing by signal peptide peptidase-like 2b (SPPL2b).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- ITM2B Truncation Promotes Migrasome Formation to Accelerate Renal Cell Carcinoma Growth.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The DNase TREX1 is a substrate of the intramembrane protease SPP with implications for disease pathogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- The transmembrane domain of Frey1 harbors a transplantable inhibitory motif for intramembrane proteases.Cellular and molecular life sciences : CMLS · 2023Article
- The role of the integral type II transmembrane protein BRI2 in health and disease.Cellular and molecular life sciences : CMLS · 2021Review
- Non-canonical Shedding of TNFα by SPPL2a Is Determined by the Conformational Flexibility of Its Transmembrane Helix.iScience · 2020Article
- Physiological functions of SPP/SPPL intramembrane proteases.Cellular and molecular life sciences : CMLS · 2020Review
- Modulating Hinge Flexibility in the APP Transmembrane Domain Alters γ-Secretase Cleavage.Biophysical journal · 2019Article
- A Functional Unfolded Protein Response Is Required for Normal Vegetative Development.Plant physiology · 2019Article
- Signal peptide peptidase-like 2c impairs vesicular transport and cleaves SNARE proteins.EMBO reports · 2019Article
- The intramembrane protease SPPL2c promotes male germ cell development by cleaving phospholamban.EMBO reports · 2019Article
- Embedded in the Membrane: How Lipids Confer Activity and Specificity to Intramembrane Proteases.The Journal of membrane biology · 2018Article
- Article
- Amyloid and intracellular accumulation of BRINeurobiology of aging · 2017Article
- Intramembrane Proteolysis of Astrotactins.The Journal of biological chemistry · 2017Article
- Article
- APP Receptor? To Be or Not To Be.Trends in pharmacological sciences · 2016Review
- Secretome analysis identifies novel signal Peptide peptidase-like 3 (Sppl3) substrates and reveals a role of Sppl3 in multiple Golgi glycosylation pathways.Molecular & cellular proteomics : MCP · 2015Article
- Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome.Frontiers in immunology · 2015Review
- Differential Inhibition of Signal Peptide Peptidase Family Members by Established γ-Secretase Inhibitors.PloS one · 2015Article
- Regulated intramembrane proteolysis of the frontotemporal lobar degeneration risk factor, TMEM106B, by signal peptide peptidase-like 2a (SPPL2a).The Journal of biological chemistry · 2014Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated intramembrane proteolysis is a widely accepted concept describing the processing of various transmembrane proteins via ectodomain shedding followed by an intramembrane cleavage. The resulting cleavage products can be involved in reverse signaling. Presenilins, which constitute the active center of the γ-secretase complex, signal peptide peptidase (SPP), and its homologues, the SPP-like (SPPL) proteases are members of the family of intramembrane-cleaving aspartyl proteases of the GXGD-type. We recently demonstrated that Bri2 (itm2b) is a substrate for regulated intramembrane proteolysis by SPPL2a and SPPL2b. Intramembrane cleavage of Bri2 is triggered by an initial shedding event catalyzed by A Disintegrin and Metalloprotease 10 (ADAM10). Additionally primary sequence determinants within the intracellular domain, the transmembrane domain and the luminal juxtamembrane domain are required for efficient cleavage of Bri2 by SPPL2b. Using mutagenesis and circular dichroism spectroscopy we now demonstrate that a high α-helical content of the Bri2 transmembrane domain (TMD) reduces cleavage efficiency of Bri2 by SPPL2b, while the presence of a GXXXG dimerization motif influences the intramembrane cleavage only to a minor extent. Surprisingly, only one of the four conserved intramembrane glycine residues significantly affects the secondary structure of the Bri2 TMD and thereby its intramembrane cleavage. Other glycine residues do not influence the α-helical content of the transmembrane domain nor its intramembrane processing.
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