What is the function of guanine exchange factors (GEFs)?
Small GTPases act as molecular switches whose effector binding depends on nucleotide state. Intrinsic exchange of GDP for GTP is extremely slow, requiring catalysts. Guanine nucleotide exchange factors bind inactive GDP-bound GTPase, distort P-loop, magnesium coordination and switch regions, lowering affinity for GDP by several orders of magnitude and permitting release. Because cytosolic GTP is roughly tenfold more abundant than GDP, GTP quickly occupies empty pocket, inducing active conformation where switch I and switch II reposition to bind effectors. Nuclear RCC1 for Ran produces high nuc
Ref: Cherfils & Zeghouf, Physiol Rev 93: 2013, GEF Mechanisms Activating Small GTPases.