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University of Geneva
A group of researchers has developed a new tool to study the structure and function of target of rapamycin complex 2 (TORC2), which helps explain why rapamycin cannot access the TOR protein in this complex.
TOR is essential for the growth of normal cells but is hyperactive in tumor cells. Rapamycin is an immunosuppressant and anticancer agent that inactivates TOR in TORC1 but not in TORC2.
“In order to more easily study TORC2, we wanted to learn how to make this complex sensitive to rapamycin,” said Robbie Loewith, PhD, of the University of Geneva in Switzerland.
So Dr Loewith and a team of scientists from Switzerland, France, and the UK set out to elucidate how TORC2 works. The team reported their findings in Molecular Cell.
Using crosslinking-mass spectrometry and electron microscopy, they discovered that TORC2 has 3 features in common with TORC1: a rhomboid shape, 2-fold symmetry, and a central cavity delimited by the interface of its protein chains.
The 2 complexes differ markedly, however, in overall size, surface area of the interface, and the volume and shape of the central cavity.
By determining the structure of TORC2, the team could observe which subunit within TORC2 was obstructing the rapamycin binding site on TOR.
“By deleting part of this subunit, we generated a variant of TORC2 sensitive to rapamycin,” said Manoel Prouteau, PhD, also of the University of Geneva.
This allowed the researchers to study how TORC2 acts to stimulate cell growth.
Now, they hope to identify a specific inhibitor of endogenous TORC2 that could also be an effective anticancer agent.
“Our discovery that TORC2 inhibition alone is sufficient to block the cell cycle suggests that mTORC2-specific inhibitors may provide new and potentially better therapeutic alternatives,” the team concluded. 
Photo courtesy of
University of Geneva
A group of researchers has developed a new tool to study the structure and function of target of rapamycin complex 2 (TORC2), which helps explain why rapamycin cannot access the TOR protein in this complex.
TOR is essential for the growth of normal cells but is hyperactive in tumor cells. Rapamycin is an immunosuppressant and anticancer agent that inactivates TOR in TORC1 but not in TORC2.
“In order to more easily study TORC2, we wanted to learn how to make this complex sensitive to rapamycin,” said Robbie Loewith, PhD, of the University of Geneva in Switzerland.
So Dr Loewith and a team of scientists from Switzerland, France, and the UK set out to elucidate how TORC2 works. The team reported their findings in Molecular Cell.
Using crosslinking-mass spectrometry and electron microscopy, they discovered that TORC2 has 3 features in common with TORC1: a rhomboid shape, 2-fold symmetry, and a central cavity delimited by the interface of its protein chains.
The 2 complexes differ markedly, however, in overall size, surface area of the interface, and the volume and shape of the central cavity.
By determining the structure of TORC2, the team could observe which subunit within TORC2 was obstructing the rapamycin binding site on TOR.
“By deleting part of this subunit, we generated a variant of TORC2 sensitive to rapamycin,” said Manoel Prouteau, PhD, also of the University of Geneva.
This allowed the researchers to study how TORC2 acts to stimulate cell growth.
Now, they hope to identify a specific inhibitor of endogenous TORC2 that could also be an effective anticancer agent.
“Our discovery that TORC2 inhibition alone is sufficient to block the cell cycle suggests that mTORC2-specific inhibitors may provide new and potentially better therapeutic alternatives,” the team concluded.
Photo courtesy of
University of Geneva
A group of researchers has developed a new tool to study the structure and function of target of rapamycin complex 2 (TORC2), which helps explain why rapamycin cannot access the TOR protein in this complex.
TOR is essential for the growth of normal cells but is hyperactive in tumor cells. Rapamycin is an immunosuppressant and anticancer agent that inactivates TOR in TORC1 but not in TORC2.
“In order to more easily study TORC2, we wanted to learn how to make this complex sensitive to rapamycin,” said Robbie Loewith, PhD, of the University of Geneva in Switzerland.
So Dr Loewith and a team of scientists from Switzerland, France, and the UK set out to elucidate how TORC2 works. The team reported their findings in Molecular Cell.
Using crosslinking-mass spectrometry and electron microscopy, they discovered that TORC2 has 3 features in common with TORC1: a rhomboid shape, 2-fold symmetry, and a central cavity delimited by the interface of its protein chains.
The 2 complexes differ markedly, however, in overall size, surface area of the interface, and the volume and shape of the central cavity.
By determining the structure of TORC2, the team could observe which subunit within TORC2 was obstructing the rapamycin binding site on TOR.
“By deleting part of this subunit, we generated a variant of TORC2 sensitive to rapamycin,” said Manoel Prouteau, PhD, also of the University of Geneva.
This allowed the researchers to study how TORC2 acts to stimulate cell growth.
Now, they hope to identify a specific inhibitor of endogenous TORC2 that could also be an effective anticancer agent.
“Our discovery that TORC2 inhibition alone is sufficient to block the cell cycle suggests that mTORC2-specific inhibitors may provide new and potentially better therapeutic alternatives,” the team concluded.