Koutnikova H, Campuzano V, Koenig M
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS, INSERM, Université Louis Pasteur, 1 rue Laurent Fries, BP 163, 67404 Illkirch Cedex-Strasbourg, France.
Hum Mol Genet. 1998 Sep;7(9):1485-9. doi: 10.1093/hmg/7.9.1485.
Frataxin is a mitochondrial protein deficient in Friedreich ataxia (FRDA) and which is associated with abnormal intramitochondrial iron handling. We identified the mitochondrial processing peptidase beta (MPPbeta) as a frataxin protein partner using the yeast two-hybrid assay. In in vitro assays, MPPbeta binds frataxin which is cleaved by the reconstituted MPP heterodimer. MPP cleavage of frataxin results in an intermediate form (amino acids 41-210) that is processed further to the mature form. In vitro and in vivo experiments suggest that two C-terminal missense mutations found in FRDA patients modulate interaction with MPPbeta, resulting in a slower maturation process at the normal cleavage site. The slower processing rate of frataxin carrying such missense mutations may therefore contribute to frataxin deficiency, in addition to an impairment of its function.
弗里德赖希共济失调（FRDA）患者体内的线粒体蛋白frataxin缺乏，且该蛋白与线粒体内铁处理异常有关。我们通过酵母双杂交试验确定线粒体加工肽酶β（MPPβ）为frataxin蛋白伴侣。在体外试验中，MPPβ与frataxin结合，而frataxin被重组的MPP异二聚体切割。frataxin经MPP切割后产生一种中间形式（氨基酸41 - 210），该中间形式会进一步加工成成熟形式。体外和体内实验表明，在FRDA患者中发现的两个C末端错义突变调节了与MPPβ的相互作用，导致正常切割位点处的成熟过程变慢。因此，携带此类错义突变的frataxin加工速率减慢，除了其功能受损外，可能还导致了frataxin缺乏。
