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== Introduction ==
== Introduction ==
 +
<Structure load='2npu' size='300' frame='true' align='right' caption='Cartoon model of the FRB domain of mTOR' scene='56/568023/2npu_cartoon_rainbow/1' />
As a member of the phosphatidylinositol kinase-related kinases(PIKK)* the mammalian targert of rapamycin (mTOR)*
As a member of the phosphatidylinositol kinase-related kinases(PIKK)* the mammalian targert of rapamycin (mTOR)*
is a multi domain protein which is involved in the regulation of cell growth and an important target of survival
is a multi domain protein which is involved in the regulation of cell growth and an important target of survival
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Due to its inhibitory effect rapamycin has been a widely used tool for studying mTOR.
Due to its inhibitory effect rapamycin has been a widely used tool for studying mTOR.
FRB is also capable of binding the activator phosphatidic acid* and small molecules, for example amino acids like
FRB is also capable of binding the activator phosphatidic acid* and small molecules, for example amino acids like
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leucine.
+
leucine.
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<Structure load='2npu' size='300' frame='true' align='right' caption='Cartoon model of the FRB domain of mTOR' scene='56/568023/2npu_cartoon_rainbow/1' />
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{{clear}}
{{clear}}
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== Residues of FRB ==
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== Structure ==
<Structure load='2npu' size='250' frame='true' align='right' caption='Insert caption here' scene='56/568023/2npu_cartoon_rainbow/1' />
<Structure load='2npu' size='250' frame='true' align='right' caption='Insert caption here' scene='56/568023/2npu_cartoon_rainbow/1' />
And now let us try to implement a scence that highlights the <scene name='56/568023/Frb_domain_acidic_alpha1_4/1'>acidic residues</scene> of the alpha 1 and alpha 4 helices of the FRB domain
And now let us try to implement a scence that highlights the <scene name='56/568023/Frb_domain_acidic_alpha1_4/1'>acidic residues</scene> of the alpha 1 and alpha 4 helices of the FRB domain

Revision as of 12:31, 1 January 2014

This Sandbox is Reserved from 06/12/2018, through 30/06/2019 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1480 through Sandbox Reserved 1543.
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FKBP12-rapamycin binding domain of mTOR

FRB domain of mTOR (or 2NPU) is responsible for the binding of the inhibitory cyclic macrolide Rapamycin


Introduction

Cartoon model of the FRB domain of mTOR

Drag the structure with the mouse to rotate

As a member of the phosphatidylinositol kinase-related kinases(PIKK)* the mammalian targert of rapamycin (mTOR)* is a multi domain protein which is involved in the regulation of cell growth and an important target of survival signals. The sequence of 2549 residues is highly conserved across eukaryotes (40-60% precent sequence identity). The protein consists of several functional domains: At the N-terminus there are 12 HEAT* repeats followed by a central FAT* domain (residue 1513 - 1910), a FRB domain (residue 2015 - 2114) a serine-threonine kinase domain (residue 2181 - 2484) and a C-terminal FATC* domain (residue 2515 - 2549). The FKBP12-rapamycin binding (FRB) domain binds the inhibitory cyclic macroloide* rapamycin in complex with the small peptidyl-prolyl cis-trans isomerase FKBP12 leading to a decreased activity of the kinase domain. Due to its inhibitory effect rapamycin has been a widely used tool for studying mTOR. FRB is also capable of binding the activator phosphatidic acid* and small molecules, for example amino acids like leucine.

Structure

Insert caption here

Drag the structure with the mouse to rotate

And now let us try to implement a scence that highlights the of the alpha 1 and alpha 4 helices of the FRB domain

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