IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
artículos
Título:
Structure of the Human ACP-ISD11 Heterodimer
Autor/es:
NOGUERA, MARTÍN EZEQUIEL; CAPECE, LUCIANA; HERRERA, MARÍA GEORGINA; AGUDELO SUÁREZ, WILLIAM ARMANDO; SANTOS, JAVIER; SEWELL, KARL ELLIOTH; KLINKE, SEBASTIÁN; NOGUERA, MARTÍN EZEQUIEL; CAPECE, LUCIANA; HERRERA, MARÍA GEORGINA; AGUDELO SUÁREZ, WILLIAM ARMANDO; SANTOS, JAVIER; SEWELL, KARL ELLIOTH; KLINKE, SEBASTIÁN
Revista:
BIOCHEMISTRY
Editorial:
AMER CHEMICAL SOC
Referencias:
Lugar: Washington; Año: 2019 vol. 58 p. 4596 - 4609
ISSN:
0006-2960
Resumen:
In recent years, the mammalian mitochondrial proteincomplex for iron−sulfur cluster assembly has been the focus of importantstudies. This is partly because of its high degree of relevance in cellmetabolism and because mutations of the involved proteins are the cause ofseveral human diseases. Cysteine desulfurase NFS1 is the key enzyme of thecomplex. At present, it is well-known that the active form of NFS1 isstabilized by the small protein ISD11. In this work, the structure of thehuman mitochondrial ACP-ISD11 heterodimer was determined at 2.0 Åresolution. ACP-ISD11 forms a cooperative unit stabilized by several ionicinteractions, hydrogen bonds, and apolar interactions. The 4′-phosphopantetheine-acyl chain, which is covalently bound to ACP, interacts with severalresidues of ISD11, modulating together with ACP the foldability of ISD11.Recombinant human ACP-ISD11 was able to interact with the NFS1desulfurase, thus yielding an active enzyme, and the NFS1/ACP-ISD11 corecomplex was activated by frataxin and ISCU proteins. Internal motions of ACP-ISD11 were studied by molecular dynamicssimulations, showing the persistence of the interactions between both protein chains. The conformation of the dimer is similarto that found in the context of the (NFS1/ACP-ISD11)2 supercomplex core, which contains the Escherichia coli ACP instead ofthe human variant. This fact suggests a sequential mechanism for supercomplex consolidation, in which the ACP-ISD11complex may fold independently and, after that, the NFS1 dimer would be stabilized.