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Three-dimensional structure determination of human MPC2 by X-ray crystallography - a mechanistic view into mitochondrial pyruvate transport

Grant number: 17/02391-8
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): May 01, 2017
Effective date (End): July 31, 2017
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Andre Luis Berteli Ambrosio
Grantee:Raghavendra Sashi Krishna Nagampalli
Supervisor abroad: Maria Isabel Abreu Ambrosio de Moraes
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brasil). Campinas , SP, Brazil
Local de pesquisa : Diamond Light Source, England  
Associated to the scholarship:14/06954-9 - Biophysical studies including X-ray structure determination of the mitochondrial pyruvate carrier (MPC) complex, BP.PD

Abstract

The active transport of glycolytic pyruvate across the human inner mitochondrial membrane (IMM) is thought to involve two mitochondrial pyruvate carrier subunits, MPC1 and MPC2, assembled as a 150 kDa oligomeric heterotypic structure. We have demonstrated that homodimeric human MPC2 can promote efficient pyruvate transport into reconstituted proteoliposomes. Importantly, the derived functional requirements and kinetic features resemble those already demonstrated for pyruvate transport in mitochondrial extracts. Our results lay the initial framework for exploring the independent role of MPC2 in homeostasis and diseases related to the dysregulation of pyruvate metabolism. However, in order to establish the molecular basis of pyruvate transport, the determination of the atomic structure of human MPC2 becomes of major importance. In this context, we propose to continue our successful collaboration with the Membrane Protein Laboratory (MPL), in order to crystallize MPC2 and collect X-ray diffraction datasets using state-of-the-art facilities and experimental approaches. The experience acquired will bring benefits back to the future endeavors of the in the field of structural biology of membrane proteins.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
KRISHNA NAGAMPALLI, RAGHAVENDRA SASHI; NECIOSUP QUESNAY, JOSE EDWIN; ADAMOSKI, DOUGLAS; ISLAM, ZEYAUL; BIRCH, JAMES; SEBINELLI, HEITOR GOBBI; BRUNO MOREIRA GIRARD, RICHARD MARCEL; RODRIGUES ASCENCAO, CAROLLINE FERNANDA; FALA, ANGELA MARIA; PAULETTI, BIANCA ALVES; CONSONNI, SILVIO ROBERTO; DE OLIVEIRA, JULIANA FERREIRA; TEIXEIRA SILVA, AMANDA CRISTINA; FRANCHINI, KLEBER GOMES; PAES LEME, ADRIANA FRANCO; SILBER, ARIEL MARIANO; CIANCAGLINI, PIETRO; MORAES, ISABEL; GOMES DIAS, SANDRA MARTHA; BERTELI AMBROSIO, ANDRE LUIS. Human mitochondrial pyruvate carrier 2 as an autonomous membrane transporter. SCIENTIFIC REPORTS, v. 8, FEB 22 2018. Web of Science Citations: 6.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.