The Rhomboid Superfamily: Structural Mechanisms and Chemical Biology Opportunities
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
30055896
DOI
10.1016/j.tibs.2018.06.009
PII: S0968-0004(18)30126-9
Knihovny.cz E-resources
- Keywords
- inhibitor, intramembrane protease, mechanism, pseudoenzyme, signaling, structure,
- MeSH
- Humans MeSH
- Membrane Proteins genetics metabolism MeSH
- ADAM17 Protein genetics metabolism MeSH
- Proteolysis * MeSH
- Signal Transduction physiology MeSH
- Tumor Necrosis Factor-alpha genetics metabolism MeSH
- Protein Transport physiology MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- ADAM17 protein, human MeSH Browser
- Membrane Proteins MeSH
- ADAM17 Protein MeSH
- Tumor Necrosis Factor-alpha MeSH
The rhomboid superfamily of transmembrane (TM) proteins includes intramembrane serine proteases and several classes of pseudoprotease. Rhomboid-like proteins occur widely across evolution and comprise biologically important regulators of fate of membrane proteins, influencing their proteolysis, trafficking, or degradation. In this review, we discuss how structural and mechanistic insights into the action of rhomboid proteases can inform on the mechanism of the pseudoproteases, and discuss the impact of structural understanding on the development of inhibitors and other chemical biology tools for these proteins. Development of modulators would be particularly relevant for the iRhoms, which are key regulators of ADAM17 and, hence, tumor necrosis factor (TNF) and epidermal growth factor receptor (EGFR) signaling, two medically important pathways.
References provided by Crossref.org
An in vitro platform for the enzymatic characterization of the rhomboid protease RHBDL4
