Efflux Pumps Represent Possible Evolutionary Convergence onto the β-Barrel Fold

Area of Science:

• Microbiology
• Structural Biology
• Evolutionary Biology

Background:

• Gram-negative bacteria possess numerous outer membrane proteins (OMPs).
• Most OMPs share a common structural motif: an up-down beta-barrel fold.
• Previous hypotheses suggested homology among most membrane beta-barrels, excluding lysins.

Purpose of the Study:

• To investigate the evolutionary origins of beta-barrels in efflux pumps.
• To determine if efflux pump beta-barrels share homology with other outer membrane beta-barrels (OMBBs) or evolved convergently.
• To explore the role of the membrane environment in protein structure evolution.

Main Methods:

• Analysis of sequence data from structurally solved OMBBs.
• Comparative structural analysis focusing on strand tilt and barrel radius.
• Grouping of OMBBs based on sequence similarity.

Main Results:

• Outer membrane factor of efflux pumps (OMEPs) exhibit distinct structural differences from other OMBBs.
• Lack of clear sequence linkage between OMEPs and other OMBBs.
• Structural and sequence similarities in the periplasmic region of OMEPs suggest a link to the periplasmic subunit of the efflux pump complex.

Conclusions:

• The beta-barrel fold in efflux pumps likely arose through convergent evolution, driven by the selective pressures of the outer membrane environment.
• Efflux pump beta-barrels are not homologous to other OMBBs.
• An evolutionary link exists between the outer membrane factor of efflux pumps and the periplasmic subunit of the same complex.