Order-disorder transitions of cytoplasmic N-termini in the mechanisms of P-type ATPases

2020 ◽  
Author(s):  
Khondker Rufaka Hossain ◽  
Daniel Clayton ◽  
Sophia C Goodchild ◽  
Alison Rodger ◽  
Richard James Payne ◽  
...  
Keyword(s):  
Protein Structure ◽  
Membrane Protein ◽  
Structure And Function ◽  
Membrane Protein Structure ◽  
Protein Structure And Function ◽  
Lipid Environment ◽  
Membrane Pumps ◽  
And Function ◽  
P Type

Membrane protein structure and function are modulated via interactions with their lipid environment. This is particularly true for the integral membrane pumps, the P-type ATPases. These ATPases play vital roles...

scholarly journals Lipid–protein interactions as determinants of membrane protein structure and function

2011 ◽  
Vol 39 (3) ◽  
pp. 767-774 ◽  
Author(s):  
William Dowhan ◽  
Mikhail Bogdanov
Keyword(s):  
Protein Structure ◽  
Membrane Protein ◽  
Transmembrane Domain ◽  
Neutral Lipids ◽  
Phospholipid Composition ◽  
Structure And Function ◽  
Membrane Protein Structure ◽  
Protein Structure And Function ◽  
Lipid Environment ◽  
And Function

To determine how the lipid environment affects membrane protein structure and function, strains of Escherichia coli were developed in which normal phospholipid composition can be altered or foreign lipids can be introduced. The properties of LacY (lactose permease) were investigated as a function of lipid environment. Assembly of LacY in membranes lacking PE (phosphatidylethanolamine) results in misorientation of the N-terminal six-TM (transmembrane domain) helical bundle with loss of energy-dependent uphill transport and retention of energy-independent downhill transport. Post-assembly introduction of PE results in nearly native orientation of TMs and restoration of uphill transport. Foreign lipids with no net charge can substitute for PE in supporting native LacY topology, but restoration of uphill transport is dependent on native topology and the proper folding of a solvent-exposed domain. Increasing the positive charge density of the cytoplasmically exposed surface of LacY counters TM misorientation in the absence of neutral lipids, demonstrating that charge interactions between these domains and the surface of the membrane bilayer are determinants of TM orientation. Therefore membrane protein organization or reorganization is determined either during initial assembly or post-insertionally through direct interactions between the protein and the lipid environment, which affects the topogenic potency of opposing charged residues as topological signals independent of the translocon.

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