Outer membrane protein design

Abstract

Membrane proteins are the gateway to the cell. These proteins are also a control center of the cell, as information from the outside is passed through membrane proteins as signals to the cellular machinery. The design of membrane proteins seeks to harness the power of these gateways and signal carriers. This review will focus on the design of the membrane proteins that are in the outer membrane, a membrane which only exists for gram negative bacteria, mitochondria, and chloroplasts. Unlike other membrane proteins, outer membrane proteins are uniquely shaped as β-barrels. Herein, I describe most known examples of membrane β-barrel design to date, focusing particularly on categorizing designs as: Firstly, structural deconstruction; secondly, structural changes; thirdly, chemical function design; and finally, the creation of new folds.

Figure 1. Anatomy of an outer membrane protein using FhuA [35] for illustration

Strands shown in yellow. Longer extracellular loops and shorter periplasmic turns shown in teal/black. The plug domain is shown in pink. Side view at left, top view and bottom view in the center, and strand view at right.

Figure 2. The three oligomeric configurations of outer membrane barrels

Each chain is colored differently. On the left is a single chain making a single barrel, OmpG [63]. In the center are three chains making three barrels, OmpF [64]. On the right is seven chains making one barrel, α-hemolysin [65].

Figure 3. Schematic of circular permutations of OmpA

The four hairpins of OmpA have each been colored differently. The permutations shift the strands on which the N- and C-termini are located, but all strands still maintain their relationship relative to each other. N and C are colored relative to the strands on which the termini are located. These permutations were found to fold and most engendered phage sensitivity. Drawn using the first pose of the OmpA NMR structure [66].

Figure 4. A split variant of OmpA

OmpA is transformed from a single-chain barrel (left) to a dual-chain barrel (right). Dual chain barrels have not yet been seen in nature. drawn using the first pose of the OmpA NMR structure [66]