RESUMEN
GTPases are molecular switches that control numerous crucial cellular processes. Unlike bona fide GTPases, which are regulated by intramolecular structural transitions, the less well studied GAD-GTPases are activated by nucleotide-dependent dimerization. A member of this family is the translocase of the outer envelope membrane of chloroplast Toc34 involved in regulation of preprotein import. The GTPase cycle of Toc34 is considered a major circuit of translocation regulation. Contrary to expectations, previous studies yielded only marginal structural changes of dimeric Toc34 in response to different nucleotide loads. Referencing PELDOR and FRET single-molecule and bulk experiments, we describe a nucleotide-dependent transition of the dimer flexibility from a tight GDP- to a flexible GTP-loaded state. Substrate binding induces an opening of the GDP-loaded dimer. Thus, the structural dynamics of bona fide GTPases induced by GTP hydrolysis is replaced by substrate-dependent dimer flexibility, which likely represents a general regulatory mode for dimerizing GTPases.
Asunto(s)
Cloroplastos/química , Guanosina Difosfato/química , Guanosina Trifosfato/química , Proteínas de la Membrana/química , Pisum sativum/química , Proteínas de Plantas/química , Precursores de Proteínas/química , Secuencia de Aminoácidos , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Cinética , Proteínas de la Membrana/genética , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas de Plantas/genética , Unión Proteica , Multimerización de Proteína , Precursores de Proteínas/genética , Transporte de Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Especificidad por Sustrato , TermodinámicaRESUMEN
Since we have learned that biological organisms like ourselves are driven by tiny biological molecular motors we try to design and produce artificial molecular motors. However, despite the huge efforts since decades, man-made artificial molecular motors are still far from biological molecular motors or macroscopic motors with regard to performance, especially with respect to energy efficiency. This review highlights recent progress towards artificial molecular motors and discusses how their design and development can be guided by the design concepts of biological molecular motors or macroscopic motors.