Madhanagopal Anandapadamanaban
Structural biologist at the MRC Laboratory of Molecular Biology who solved the structure of the human Rag GTPases bound to mTORC1, showing how amino acids bring mTORC1 to the lysosome
Investigator Scientist, MRC Laboratory of Molecular Biology, Cambridge (Roger Williams group, papers since 2017) · PhD, Linköping University, Sweden (Maria Sunnerhagen group, papers 2013–2015)
Roger Williams group, MRC Laboratory of Molecular Biology (Cambridge, England, United Kingdom) ↗
mTORC1 can only be switched on at the surface of lysosomes. It gets there by binding to the Rag GTPases, a pair of small proteins that act like a switch: each can hold either GTP or GDP, and the pair changes shape depending on which. When amino acids are plentiful, the Rags take on one particular combination and grab mTORC1. Madhanagopal Anandapadamanaban's 2019 Science paper (ANA2019), from Roger Williams' group at the MRC Laboratory of Molecular Biology in Cambridge, used cryo-electron microscopy and X-ray crystallography to see this at near-atomic detail. The structures showed which surfaces of the Rag pair touch the Raptor subunit of mTORC1 and explained why only the active nucleotide state binds.
This gave a physical picture of the first step in amino-acid sensing by mTORC1, which until then had been known mainly from genetics and biochemistry. It was done with purified human proteins.
Anandapadamanaban did doctoral work at Linköping University in Sweden on structures of proteins that control transcription and ubiquitination, including a 2013 Nature Structural and Molecular Biology paper on the TATA-binding protein bound to TAF1. At the LMB the work has stayed with mTOR and its relatives: a 2017 review with Williams on how TORC1 is activated by nutrients, a 2021 eLife study on how the inhibitor protein DEPTOR binds mTOR, and a 2024 review on the activation of PI3K-family enzymes. The Cambridge cancer centre lists Anandapadamanaban as an Investigator Scientist at the LMB.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2019 | M | Architecture of human Rag GTPase heterodimers and their complex with mTORC1 ANA2019 First author: solved the cryo-EM and crystal structures of the human Rag GTPase pair alone and bound to mTORC1. |
Co-authors in the Atlas 5
People with a profile here who share at least one study with Madhanagopal Anandapadamanaban.
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- Alex Berndt Protein scientist in Roger Williams' group at the MRC Laboratory of Molecular Biology who helped solve structures of PI3K enzymes and of mTOR and its partners
- David M. Sabatini Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
- Christopher Johnson Biophysicist who built and ran the Biophysics Facility at the MRC Laboratory of Molecular Biology, measuring how proteins fold, bind and change shape for dozens of research groups
- Kacper B. Rogala Solved the near-atomic cryo-EM structure that shows how mTORC1 physically docks at the lysosome by reading the Rag GTPases
- Roger L. Williams Solved structures showing how the Rag GTPases bind mTORC1 and how TOR forms a dimer, working at the MRC Laboratory of Molecular Biology
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