Pan J Y, Wessling-Resnick M
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Bioessays. 1998 Jun;20(6):516-21. doi: 10.1002/(SICI)1521-1878(199806)20:6<516::AID-BIES11>3.0.CO;2-3.
GTPases share highly conserved guanine nucleotide-binding domains and fulfill diverse functions through a common molecular switch. An inactive GDP-bound protein is turned on by a guanine nucleotide exchange factor (GEF) that catalyzes exchange of GTP for GDP, but unfortunately little is known about the mechanism of GEF action. A common mechanism for GDP/GTP exchange can be envisioned wherein GEFs activate monomeric GTPases through transient disruption of Mg2+ coordination in the nucleotide-binding pocket while stabilizing a nucleotide-free (and cation-free) conformation. After guanine nucleotide exchange, Mg2+ coordination is restored to complete the conformational switch to the active GTP-bound state. Evidence in the literature highlighting an important regulatory role for Mg2+ in the mechanism of GEF-mediated GDP/GTP exchange by monomeric GTPases is summarized.
GTP酶具有高度保守的鸟嘌呤核苷酸结合结构域，并通过一个共同的分子开关履行多种功能。无活性的结合GDP的蛋白被鸟嘌呤核苷酸交换因子（GEF）激活，GEF催化GTP与GDP的交换，但遗憾的是，关于GEF作用机制的了解甚少。可以设想一种GDP/GTP交换的常见机制，即GEF通过暂时破坏核苷酸结合口袋中Mg2+的配位作用来激活单体GTP酶，同时稳定无核苷酸（且无阳离子）的构象。鸟嘌呤核苷酸交换后，Mg2+配位得以恢复，从而完成向活性GTP结合状态的构象转换。本文总结了文献中强调Mg2+在单体GTP酶介导的GEF依赖性GDP/GTP交换机制中重要调节作用的证据。
