ГТФазы: структура, функции и регуляция активности.

Class of enzymes
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. 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. In the generalized receptor transducer effector signaling model of Martin Rodbell, signaling GTPases act as transducers to regulate the activity of effector proteins. Some GTPases have little to no intrinsic GTPase activity, and are entirely dependent on GAP proteins for deactivation (such as the ADP ribosylation factor or ARF family of small GTP binding proteins that are involved in vesicle mediated transport within cells). To become activated, GTPases must bind to GTP. Since mechanisms to convert bound GDP directly into GTP are unknown, the inactive GTPases are induced to release bound GDP by the action of distinct regulatory proteins called guanine nucleotide exchange factors or GEFs. The amount of active GTPase can be changed in several ways:
Acceleration of GDP dissociation by GEFs speeds up the accumulation of active GTPase. Inhibition of GDP dissociation by guanine nucleotide dissociation inhibitors (GDIs) slows down accumulation of active GTPase. Acceleration of GTP hydrolysis by GAPs reduces the amount of active GTPase. Artificial GTP analogues like GTP γ S, β,γ methylene GTP, and β,γ imino GTP that cannot be hydrolyzed can lock the GTPase in its active state. Mutations (such as those that reduce the intrinsic GTP hydrolysis rate) can lock the GTPase in the active state, and such mutations in the small GTPase Ras are particularly common in some forms of cancer.

In most GTPases, the specificity for the base guanine versus other nucleotides is imparted by the base recognition motif, which has the consensus sequence [N/T]KXD. The following classification is based on shared features; some examples have mutations in the base recognition motif that shift their substrate specificity, most commonly to ATP.

The TRAFAC class of G domain proteins is named after the prototypical member, the translation factor G proteins. They play roles in translation, signal transduction, and cell motility. and class 2 release factors. Other members include EF 4 (LepA), BipA (TypA), SelB (bacterial selenocysteinyl tRNA EF Tu paralog), Tet (tetracycline resistance by ribosomal protection), and HBS1L (eukaryotic ribosome rescue protein similar to release factors). The superfamily also includes the Bms1 family from yeast. The alpha subunits contain the GTP binding/GTPase domain flanked by long regulatory regions, while the beta and gamma subunits form a stable dimeric complex referred to as the beta gamma complex. When activated, a heterotrimeric G protein dissociates into activated, GTP bound alpha subunit and separate beta gamma subunit, each of which can perform distinct signaling roles. Heterotrimeric G proteins act as the transducers of G protein coupled receptors, coupling receptor activation to downstream signaling effectors and second messengers. In unstimulated cells, heterotrimeric G proteins are assembled as the GDP bound, inactive trimer (Gα GDP Gβγ complex).

Small GTPases function as monomers and have a molecular weight of about 21 kilodaltons that consists primarily of the GTPase domain. They are also called small or monomeric guanine nucleotide binding regulatory proteins, small or monomeric GTP binding proteins, or small or monomeric G proteins, and because they have significant homology with the first identified such protein, named Ras, they are also referred to as Ras superfamily GTPases. Small GTPases generally serve as molecular switches and signal transducers for a wide variety of cellular signaling events, often involving membranes, vesicles or cytoskeleton.

For a discussion of Translocation factors and the role of GTP, see signal recognition particle (SRP).

While tubulin and related structural proteins also bind and hydrolyze GTP as part of their function to form intracellular tubules, these proteins utilize a distinct tubulin domain that is unrelated to the G domain used by signaling GTPases. There are also GTP hydrolyzing proteins that use a P loop from a superclass other than the G domain containg one. Examples include the NACHT proteins of its own superclass and McrB protein of the AAA+ superclass.