GTPbinding

GTPbinding refers to the property of certain proteins to bind guanosine triphosphate (GTP). This capability is central to the GTPase superfamily, whose members act as molecular switches that cycle between active GTP-bound and inactive GDP-bound states. The GTP-binding site is typically contained within a conserved GTPase domain that undergoes conformational changes upon nucleotide binding and hydrolysis.

Structure and mechanism: Many GTPbinding proteins belong to the P-loop NTPase superfamily, featuring motifs such as the Walker A (P-loop) that coordinates phosphate groups and a magnesium ion. The switch regions of the protein change shape depending on whether GTP or GDP is bound, enabling interactions with effector proteins. Intrinsic GTPase activity can be accelerated by GAPs (GTPase-activating proteins), while GEFs (guanine nucleotide exchange factors) promote the release of GDP in exchange for GTP, resetting the cycle. Some GTPbinding proteins are further regulated by GDIs (GDP-dissociation inhibitors) that sequester them in the cytosol.

Functions: GTPbinding proteins participate in a wide range of cellular processes. Small GTPases such as Ras, Rho, Rab, Arf, and Ran regulate cell growth, cytoskeletal organization, vesicular trafficking, and nuclear transport. Heterotrimeric G proteins transduce signals from cell-surface receptors. GTP-binding is also essential in protein synthesis (e.g., translation factors like EF-Tu and EF-G) and in microtubule dynamics (tubulin binds GTP).

Regulation and significance: Proper cycling between GTP- and GDP-bound states is crucial for accurate signaling and cellular organization. Dysregulation can contribute to diseases, notably oncogenic mutations in Ras that impair GTP hydrolysis. GTPbinding proteins are common targets for research and therapeutic development in cancer, neurological disorders, and infectious diseases.

Evolution and terminology: The use of GTP as a molecular switch is ancient and widespread across life, reflected in diverse GTPbinding proteins that share a conserved nucleotide-binding fold and switch mechanism.