BIOC 212 Lecture Notes - Lecture 20: Alpha Helix, Membrane Potential, Beta Barrel
29 May 2018
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9- Intracellular Trafficking
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IM Integral-Signal Receptor
• TOM70 receptor assists IM proteins with integral signals
o Send proteins specifically into IM
• Has different pattern of signals
o TOM70 itself has TM anchor and region that recognizes targeting signals
• Most of proteins that use this pathway are metabolite carriers;
o Family of 6-TM domains proteins
o Hydrophobic TM helices act as the targeting signal for TOM70 pathway
o Other large hydrophobic proteins with multiple TM helices that use TOM70 as
well
• C-terminal domain (green) recognizes targeting signal
• Central TPR co-chaperone domain binds Hsc70 or Hsp90
o Have a TPR co-chaperone domain between TM anchor and signal
recognition domain
TOM70 Mechanism
• Proteins are fairly hydrophobic, have multiple TM anchors
• Before import, when in cytosol, are bound by chaperones (Hsp70/90)
o But the chaperones are not specific for the targeting sequences, just
recognize them as typical unfolded protein
o Not providing targeting information, that is coming from TOM70
• Chaperones keep IM precursors soluble before import, but do not recognize
targeting signal
o Have complex of chaperones bound to precursor polypeptide
o Chaperones dock onto TOM70 TPR domain
§ Hsp70 & Hsp90 have EEVD motif
• Internal signals are presented to TOM70 C-terminal domain and are recognized
o Docking brings targeting signal closer to TOM70 receptor, which then
recognizes the targeting signal
• ATPase cycles of chaperones transfer protein to TOM40 pore and a transporter in
the IMS (TIM9/TIM10)
o Because chaperones are always cycling ATP, are always coming on and off
the polypeptides
§ Once have complex of chaperones with TOM70, the next time go
through ATP cycle, chaperones will let go and polypeptide can go
forward into TOM40 pore
