IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Rescuing the rescuer: on interaction between ISD11 and the Mitochonrial Acyl Carrier protein
Autor/es:
HERRERA MG; SANTOS J; PIGNATARO MF; NOGUERA ME
Lugar:
La Plata, Buenos Aires
Reunión:
Congreso; Reunión Anual de la Sociedad Argentina de Biofísica; 2018
Institución organizadora:
SAB
Resumen:
Rescuing the rescuer: on interaction between ISD11 and the Mitochonrial Acyl Carrier protein.M.G. Herrera1,2, M.F. Pignataro1,2, M. E. Noguera1,2 and J. Santos1,2.1 Instituto de Química y Fisicoquímica Biológicas, Dr. Alejandro Paladini (UBA-CONICET).2 Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, Argentina. Iron-sulfur clusters are essential cofactors in many biochemical processes [1]. ISD11, one of the subunits of the protein complex that carries out the cluster assembly in mitochondria, is necessary 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 interactions, but also by means of a long chain acyl group which is bound to the residue Ser36 of ACP by the phosphopantetheine moiety. This molecule 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 de mitochondrial mature human ACP form, and this may favors ISD11 solubility and reduce its aggregation prone tendency. We carried out the co-expression of human mitochondrial ACP and ISD11 in E. coli. This work showed that the human ACP and ISD11 recognize each other and form a soluble, structured and stable complex which is able to bind to the human NFS1 subunit modulating its activity. Also, we started to study the structure of the ACP-ISD11 complex by X-ray 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. Friemel, 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. Rescuing the rescuer: on interaction between ISD11 and the Mitochonrial Acyl Carrier protein.M.G. Herrera1,2, M.F. Pignataro1,2, M. E. Noguera1,2 and J. Santos1,2.1 Instituto de Química y Fisicoquímica Biológicas, Dr. Alejandro Paladini (UBA-CONICET).2 Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, Argentina. Iron-sulfur clusters are essential cofactors in many biochemical processes [1]. ISD11, one of the subunits of the protein complex that carries out the cluster assembly in mitochondria, is necessary 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 interactions, but also by means of a long chain acyl group which is bound to the residue Ser36 of ACP by the phosphopantetheine moiety. This molecule 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 de mitochondrial mature human ACP form, and this may favors ISD11 solubility and reduce its aggregation prone tendency. We carried out the co-expression of human mitochondrial ACP and ISD11 in E. coli. This work showed that the human ACP and ISD11 recognize each other and form a soluble, structured and stable complex which is able to bind to the human NFS1 subunit modulating its activity. Also, we started to study the structure of the ACP-ISD11 complex by X-ray 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. Friemel, 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.