Mtor

• TOR proteine
• rgdiff species
• 1. TOR. Introduction
• lectural week part1.
• 1. TOR


  Mechanism/mechaniche target of
• known as the master regulated for cell signalling.
• Where did the come from?

  1. Scientists conducted or late research study in South Ameria, the region was called rapanoi

  2. Collected oil samples & trying to find novel antimicrobial agents

  3. The results collected mere taken to lab/islated a bacteria from Sample 1

  4. Bacterial sample showed marly properties such as anti-hayal, anti burer and immunosupressant

  5. Compound named as rapamycin (good example of bottom-up scientific discovery!)
• Further analysis on cape ausch

  1. Showed that it acted in part by forming a complex with an enzyme FKBP12/ this is a peptadyliscence

  2. Both the FKBP12 and Rapamycin complex inhibits righel transduction pathway required for normal cell growth and prolifection
• Structure of mTOR


  • It has several functional domains
  • FAT FRBIRD (FATC) region acts at the huminal Ferminus as an interaction domain allowing TOR to form prstenprointeractions
  • There are 20 tanity arranged heat repeats of which have alpha helixes
  • At the Clerminal end, there's a kinase dens nat to the fat feminalis The FAS Sermine which has a sequeme similarity with the catalytic subunit of P
• The binding of FKBPI
• NRD demain containe
• Enakeded in the catalytic domain, pharma and coauneufatere ofsale demain and required for mTOR activity of the cell
• Awi auidy fat v plespherighted by ter enzyme
• mTOR Structure


  • The most distinct feature to distinguish blu mTORC1 and mTORC2 is cuz most reliable
  • mTORC1 inhibited by rapamacia has its effect on the FRB
  • MTOKE 2 retracted by rapamycin activity!
  • Due to chronic effects if left for longer time period it will have an effect (inhibitory) on mTORC2 as well
• 1. TOR Complexes


  1. mTORC1 and MTORC2, similarities and differences

  2. mTORC1 rather than md shows inhibition to the rap miện FKBP12 and the

  3. mTORC1 is defined by it's Smain complexes: the 13 complexes.r Tor ptor protein

  4. The approbin is tocilitates the recruitment of the different notor Bushrales 4g back to the complexe

  5. This is the chronic exposure, they have new compres allows the sho TORRE to OCCUR

  6. If cell, arged Freatount with mTORC2 also the mice Rivase + abe contains rictor plein

  7. Function of recruiting the, Kinesse also affects the find metaket and glucose metabolium
• Activation of mTORC1 by Rheb

  1. The factor functions as a GAP protein or the GAP for the small GTPases Rheb

  2. Rheb's directly binds to mTORC1

  3. In the 5 prime end the ELFYE is produced and phosphorylated

  4. The S6K activates the imloRes + inhibit the 4EBP pathway

  5. You get downstream signalling of the mTORES

  6. MTORC2 on the other hand will be more activated, makes the bubs to go away that slave the pathways
• The Rhebo GTPase


  • Positive feedback trop OFF GOP GTPase GAP GEF Achah Guanine neucleotide Protein Exchange Easter ON GTP Dexian GTP (Active)
  • The small GTPases continue to cycle b)win active GDP bound forms + activate GTP bound forms
  • Also regulated by GAP that pronates the GDP bound or the inactive form of small GTPases
• Activation of mTORC1 by Rheb

  1. Growth factor signalling leads to the phosphorylation of TSC complex and inhibits the gp GAP activity

  2. Rheb an activator of mTOR 1 and leads to the activation

  3. Note: Cheb is usually te thared to the lysosome or mabware within the cell and this adds a special regulation of mTOR activation
• Negative regulation of mTRACS by AN AMPK


  1. This also activates the chress release lemoses

  2. Allows phosphonation is activating the activity
• Regulation of mTORC2


  1. mTORC2 activated by insulin signalling via the P13 kinases

  2. In the absence of insulin the MITORC will be deactivated
• mTOR downstream signalling and Disease

  1. mTORC1 is essential be regulating the balance in anabolism and cabilism in an

  2. Cells need to increase the anabolic Pathways of things like proteins

  3. They also need to supress the catabolic pathways

  4. RNA processing forms the cap structure

  5. Eukaryotic mRNAs are 1st transcribed as transcript, further processed to form mature mRNA by splicing out the non tronic Sequences

  6. Cap structures important in protein translation because we need to cap structure to recreate the ribosomal mRNA to allow protein translation to initiate
• Downstream signalling by mTORC2

  1. mTORC2 controls cell proliferation through the cell

  2. Slak 1 will regulate iron transport & cell dividal

  3. The most important side of mTORC2 is the phosphorylation and activation of ART a downstream effector of down signalling

  4. Provides negative feed back by phosphorylating AKT activity promotes cell survival and growth by phosphorylating and inhibiting several key substrates
• TORC Signalling in disease