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Your search keyword '"Madan Mohan, Pooja"' showing total 8 results
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8 results on '"Madan Mohan, Pooja"'

2. Allosteric control of dynamin-related protein 1 through a disordered C-terminal Short Linear Motif

Author

Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), European Commission, Eusko Jaurlaritza, Pérez-Jover, Isabel, Rochon, Kristy, Hu, Di, Mahajan, Mukesh, Madan Mohan, Pooja, Santos-Pérez, Isaac, Ormaetxea Gisasola, Julene, Martínez Gálvez, Juan Manuel, Agirre, Jon, Qi, Xin, Mears, Jason A., Shnyrova, Anna V., Ramachandran, Rajesh, Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), European Commission, Eusko Jaurlaritza, Pérez-Jover, Isabel, Rochon, Kristy, Hu, Di, Mahajan, Mukesh, Madan Mohan, Pooja, Santos-Pérez, Isaac, Ormaetxea Gisasola, Julene, Martínez Gálvez, Juan Manuel, Agirre, Jon, Qi, Xin, Mears, Jason A., Shnyrova, Anna V., and Ramachandran, Rajesh

Abstract

The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure and function in vitro and in vivo. Extension of the CT-SLiM by non-native residues, or its interaction with the protein partner GIPC-1, constrains Drp1 subunit conformational dynamics, alters self-assembly properties, and limits cooperative GTP hydrolysis, surprisingly leading to the fission of model membranes in vitro. In vivo, the involvement of the native CT-SLiM is critical for productive mitochondrial and peroxisomal fission, as both deletion and non-native extension of the CT-SLiM severely impair their progression. Thus, contrary to prevailing models, Drp1-catalyzed membrane fission relies on allosteric communication mediated by the CT-SLiM, deceleration of GTPase activity, and coupled changes in subunit architecture and assembly-disassembly dynamics.

Published
2024

5. Reply to Roy and Pucadyil: A gain of function by a GTPase-impaired Drp1

Author

Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Universidad del País Vasco, National Institutes of Health (US), Pérez-Jover, Isabel [0000-0002-0288-7931], Ramachandran, Rajesh [0000-0002-4645-2841], Shnyrova, Anna V. [0000-0002-5329-348X], Pérez-Jover, Isabel, Madan Mohan, Pooja, Ramachandran, Rajesh, Shnyrova, Anna V., Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Universidad del País Vasco, National Institutes of Health (US), Pérez-Jover, Isabel [0000-0002-0288-7931], Ramachandran, Rajesh [0000-0002-4645-2841], Shnyrova, Anna V. [0000-0002-5329-348X], Pérez-Jover, Isabel, Madan Mohan, Pooja, Ramachandran, Rajesh, and Shnyrova, Anna V.

Published
2022

6. NMR identification of a conserved Drp1 cardiolipin-binding motif essential for stress-induced mitochondrial fission

Author

Mahajan, Mukesh, primary, Bharambe, Nikhil, additional, Shang, Yutong, additional, Lu, Bin, additional, Mandal, Abhishek, additional, Madan Mohan, Pooja, additional, Wang, Rihua, additional, Boatz, Jennifer C., additional, Manuel Martinez Galvez, Juan, additional, Shnyrova, Anna V., additional, Qi, Xin, additional, Buck, Matthias, additional, van der Wel, Patrick C. A., additional, and Ramachandran, Rajesh, additional

Published
2021
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7. NMR identification of a conserved Drp1 cardiolipin-binding motif essential for stress-induced mitochondrial fission

Author

National Institutes of Health (US), Achievement Rewards for College Scientists Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Eusko Jaurlaritza, Universidad del País Vasco, Mahajan, Mukesh, Bharambe, Nikhil, Shang, Yutong, Lu, Bin, Mandal, Abhishek, Madan Mohan, Pooja, Wang, Rihua, Boatz, Jennifer C., Martínez Gálvez, Juan Manuel, Shnyrova, Anna V., Qi, Xin, Buck, Matthias, Wel, Patrick C. A. van der, Ramachandran, Rajesh, National Institutes of Health (US), Achievement Rewards for College Scientists Foundation, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Eusko Jaurlaritza, Universidad del País Vasco, Mahajan, Mukesh, Bharambe, Nikhil, Shang, Yutong, Lu, Bin, Mandal, Abhishek, Madan Mohan, Pooja, Wang, Rihua, Boatz, Jennifer C., Martínez Gálvez, Juan Manuel, Shnyrova, Anna V., Qi, Xin, Buck, Matthias, Wel, Patrick C. A. van der, and Ramachandran, Rajesh

Abstract

Mitochondria form tubular networks that undergo coordinated cycles of fission and fusion. Emerging evidence suggests that a direct yet unresolved interaction of the mechanoenzymatic GTPase dynamin-related protein 1 (Drp1) with mitochondrial outer membrane-localized cardiolipin (CL), externalized under stress conditions including mitophagy, catalyzes essential mitochondrial hyperfragmentation. Here, using a comprehensive set of structural, biophysical, and cell biological tools, we have uncovered a CL-binding motif (CBM) conserved between the Drp1 variable domain (VD) and the unrelated ADP/ATP carrier (AAC/ANT) that intercalates into the membrane core to effect specific CL interactions. CBM mutations that weaken VD-CL interactions manifestly impair Drp1-dependent fission under stress conditions and induce "donut" mitochondria formation. Importantly, VD membrane insertion and GTP-dependent conformational rearrangements mediate only transient CL nonbilayer topological forays and high local membrane constriction, indicating that Drp1-CL interactions alone are insufficient for fission. Our studies establish the structural and mechanistic bases of Drp1-CL interactions in stress-induced mitochondrial fission.

Published
2021

8. A Single Common Protocol for the Expression and Purification of Soluble Mammalian DSPs from Escherichia coli.

Author

Stepanyants N, Macdonald PJ, Madan Mohan P, and Ramachandran R

Subjects
Animals, Escherichia coli metabolism, Plasmids genetics, Solubility, Transformation, Bacterial, Desmoplakins genetics, Desmoplakins isolation & purification, Escherichia coli genetics, Gene Expression, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins isolation & purification
Abstract

Mammalian DSPs have been historically isolated either from native tissue sources or from transfected insect cell cultures via time-consuming and cumbersome protocols often yielding protein of variable quality and quantity. A facile and highly reproducible alternative methodology involving the heterologous expression and purification of soluble mammalian DSPs from E. coli, which yields highly active and functional protein of a uniform quality and quantity, free of spurious posttranslational modifications inherent to mammalian and insect cell expression systems, is described in this chapter.

Published
2020
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