Quality control of integral membrane proteins.
Integral membrane proteins (IMPs) are essential components of the plasma and organellar membranes of the eukaryotic cell. Non-native IMPs, which can arise as a result of mutations, errors during biosynthesis or cellular stress, can disrupt these membranes and potentially lead to cell death. To protect against this outcome, the cell possesses quality control (QC) systems that detect and dispose of non-native IMPs from cellular membranes. Recent studies suggest that recognition of non-native IMPs by the QC machinery is correlated with the thermodynamic stability of these proteins. Consistent with this, small molecules known as chemical and pharmacological chaperones have been identified that stabilize non-native IMPs and enable them to evade QC. These findings have far-reaching implications for treating human diseases caused by defective IMPs.
Krebs
Mark P
MP
Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, FL 32610, USA. mpkrebs@ufl.edu
Noorwez
Syed M
SM
Malhotra
Ritu
R
Kaushal
Shalesh
S
D002462:Cell Membrane / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D008954:Models, Biological; D018832:Molecular Chaperones; D017510:Protein Folding; D011786:Quality Control
D008565:Membrane Proteins; D018832:Molecular Chaperones