GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a protein domain common to many GTPases.
GTPases function as molecular switches or timers in many fundamental cellular processes.
Examples of these roles include:
Signal transduction in response to activation of cell surface receptors, including transmembrane receptors such as those mediating taste, smell and vision.
Protein biosynthesis (a.k.a. translation) at the ribosome.
Regulation of cell differentiation, proliferation, division and movement.
Translocation of proteins through membranes.
Transport of vesicles within the cell, and vesicle-mediated secretion and uptake, through GTPase control of vesicle coat assembly.
GTPases are active when bound to GTP and inactive when bound to GDP. In the generalized receptor-transducer-effector signaling model of Martin Rodbell, signaling GTPases act as transducers to regulate the activity of effector proteins. This inactive-active switch is due to conformational changes in the protein distinguishing these two forms, particularly of the "switch" regions that in the active state are able to make protein-protein contacts with partner proteins that alter the function of these effectors.
Hydrolysis of GTP bound to an (active) G domain-GTPase leads to deactivation of the signaling/timer function of the enzyme. The hydrolysis of the third (γ) phosphate of GTP to create guanosine diphosphate (GDP) and Pi, inorganic phosphate, occurs by the SN2 mechanism (see nucleophilic substitution) via a pentavalent transition state and is dependent on the presence of a magnesium ion Mg2+.
GTPase activity serves as the shutoff mechanism for the signaling roles of GTPases by returning the active, GTP-bound protein to the inactive, GDP-bound state. Most "GTPases" have functional GTPase activity, allowing them to remain active (that is, bound to GTP) only for a short time before deactivating themselves by converting bound GTP to bound GDP.
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Presentation of selected signalling pathways with emphasis on both the mechanism of action of the molecules involved, molecular interactions and the role of their spatio-temporal organization within t
Le but du cours est de fournir un aperçu général de la biologie des cellules et des organismes. Nous en discuterons dans le contexte de la vie des cellules et des organismes, en mettant l'accent sur l
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of enzymes called GTPases.
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Most commonly, protein phosphorylation is catalyzed by protein kinases, ultimately resulting in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway.
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first messengers and second messengers, are classified as autocrine, juxtacrine, paracrine, and endocrine depending on the range of the signal.) Second messengers trigger physiological changes at cellular level such as proliferation, differentiation, migration, survival, apoptosis and depolarization.
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