The lipid bilayer strengthens the cooperative network of membrane proteins.

Membrane proteins fold and function in a lipid bilayer constituting cell membranes. Nonetheless, their structure and function can be recapitulated in diverse amphiphilic assemblies whose compositions deviate from native membranes. It remains unclear how various hydrophobic environments stabilize membrane proteins and whether lipids play any unique role in protein stability compared to other types of amphiphiles.

Lipid bilayer strengthens the cooperative network of membrane proteins.

Although membrane proteins fold and function in a lipid bilayer constituting cell membranes, their structure and functionality can be recapitulated in diverse amphiphilic assemblies whose compositions deviate from native membranes. It remains unclear how various hydrophobic environments can stabilize membrane proteins and whether lipids play any role therein. Here, using the evolutionary unrelated α-helical and β-barrel membrane proteins of , we find that the hydrophobic thickness and the strength of amphiphile- amphiphile packing are critical environmental determinants of membrane protein stability.

Lipid bilayer induces contraction of the denatured state ensemble of a helical-bundle membrane protein.

Defining the denatured state ensemble (DSE) and disordered proteins is essential to understanding folding, chaperone action, degradation, and translocation. As compared with water-soluble proteins, the DSE of membrane proteins is much less characterized. Here, we measure the DSE of the helical membrane protein GlpG of () in native-like lipid bilayers.

Proteolysis mediated by the membrane-integrated ATP-dependent protease FtsH has a unique nonlinear dependence on ATP hydrolysis rates.

ATPases associated with diverse cellular activities (AAA+) proteases utilize ATP hydrolysis to actively unfold native or misfolded proteins and translocate them into a protease chamber for degradation. This basic mechanism yields diverse cellular consequences, including the removal of misfolded proteins, control of regulatory circuits, and remodeling of protein conformation. Among various bacterial AAA+ proteases, FtsH is only membrane-integrated and plays a key role in membrane protein quality control.

Folding-Degradation Relationship of a Membrane Protein Mediated by the Universally Conserved ATP-Dependent Protease FtsH.

ATP-dependent protein degradation mediated by AAA+ proteases is one of the major cellular pathways for protein quality control and regulation of functional networks. While a majority of studies of protein degradation have focused on water-soluble proteins, it is not well understood how membrane proteins with abnormal conformation are selectively degraded. The knowledge gap stems from the lack of an in vitro system in which detailed molecular mechanisms can be studied as well as difficulties in studying membrane protein folding in lipid bilayers.