Rescuing the rescuer: on interaction between ISD11 and the Mitochondrial Acyl Carrier protein

HERRERA, MARÍA GEORGINA; PIGNATARO, MARÍA FLORENCIA; NOGUERA, MARTÍN EZEQUIEL; SANTOS, JAVIER

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; 2018

Iron-sulfur clusters are essential cofactors in many biochemical processes [1]. ISD11, one of the subunits of the protein complex that carries out cluster assembly in mitochondria, is necessari for cysteine desulfurase NFS1 stability and function [2, 3]. Several authors have recently provided evidence showing that in the recombinant complex expressed in E. coli, ISD11 interacts with the acyl carrier protein (ACP) from this microorganism. This interaction may stabilize ISD11 which is a protein that tends to aggregate when it is isolated. Interestingly, in this complex, ACP interacts with ISD11, not only by electrostatic interactios, but also by means of a long chain acyl group which is bound to Ser36 of ACP by the phosphopantetheine moiety. This molecula intercalates in the core of ISD11 and interacts with the three alpha helices of ISD11 [4, 5]. Considering these results, we decided to evaluate if ISD11 is able to generate a stable complex with the mitochondrial mature human ACP (hACP) form, and this may favors ISD11 solubility and reduce its aggregation prone tendency. We carried out the coexpression of hACP and ISD11 in E. coli. This work showed that hACP and ISD11 recognize each othere and form soluble, structured and stable complex which is able to bind to he human NFS1 subunit modulating its activity. Also, we started to study the structure of the hACP-ISD11 complex by X-rat crystallography, obtaining promising results. These findings offer the opportunity of evaluating the mechanism of interaction between ISD11 and NFS1 by biophysical, computational and biochemical tools.[1] L.K. Beilschmidt, H.M. Puccio, Biochimie, 100 (2014) 48-60.[2] H. Angerer, Biology (Basel), 4 (2015) 133-150.[3] S.C. Lim, M. Freimel, J.E. Marum, E.J, et al, Hum Mol Genet, 22 (2013) 4460-4473.[4] S.A. Cory, J.G. Van Vranken, E.J. Brignole, et al, Proc Natl Acad Sci U S A, 114 (2017) E5325-E5334.[5] M.T. Boniecki, S.A. Freibert, U. Muhlenhoff, et al, Nat Commun, 8 (2017) 1287.AcknowledgmentsThis study was supported by the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT PICT2013 Nro.0983), the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), the Universidad de Buenos Aires (UBACyT21014 20020130100468BA) and FARA, Friedreich's Ataxia Research Alliance