Protein–membrane interactions in small GTPase signalling and pharmacology: perspectives from Arf GTPases studies
| Autor: | Jacqueline Cherfils, Mahel Zeghouf, Agata Nawrotek |
|---|---|
| Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
[SDV]Life Sciences [q-bio]
GTPase Biology Biochemistry GTP Phosphohydrolases 03 medical and health sciences 0302 clinical medicine Cell Movement Drug Discovery Protein Interaction Mapping Animals Guanine Nucleotide Exchange Factors Humans Small GTPase Cytoskeleton Monomeric GTP-Binding Proteins 030304 developmental biology 0303 health sciences Binding Sites Membrane Glycoproteins Effector Drug discovery Cell Membrane GTPase-Activating Proteins Proteins Lipids Small molecule 3. Good health Protein Transport Signalling Structural biology Drug Design ADP-Ribosylation Factor 1 Sulfotransferases Signal transduction Dimerization Neuroscience 030217 neurology & neurosurgery Protein Binding Signal Transduction |
| Zdroj: | Biochemical Society Transactions Biochemical Society Transactions, Portland Press, 2020, 48 (6), pp.2721-2728. ⟨10.1042/BST20200482⟩ |
| ISSN: | 0300-5127 1470-8752 |
| DOI: | 10.1042/BST20200482⟩ |
| Popis: | International audience; Small GTPases, in association with their GEFs, GAPs and effectors, control major intracellular processes such as signal transduction, cytoskeletal dynamics and membrane trafficking. Accordingly, dysfunctions in their biochemical properties are associated with many diseases, including cancers, diabetes, infections, mental disorders and cardiac diseases, which makes them attractive targets for therapies. However, small GTPases signalling modules are not well-suited for classical inhibition strategies due to their mode of action that combines protein–protein and protein–membrane interactions. As a consequence, there is still no validated drug available on the market that target small GTPases, whether directly or through their regulators. Alternative inhibitory strategies are thus highly needed. Here we review recent studies that highlight the unique modalities of the interaction of small GTPases and their GEFs at the periphery of membranes, and discuss how they can be harnessed in drug discovery. |
| Databáze: | OpenAIRE |
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