The structural biology of β-barrel membrane proteins: a summary of recent reports

Abstract

The outer membranes of Gram-negative bacteria, mitochondria, and chloroplasts all contain transmembrane β-barrel proteins. These β-barrel proteins serve essential functions in cargo transport and signaling and are also vital for membrane biogenesis. They have also been adapted to perform a diverse set of important cellular functions including acting as porins, transporters, enzymes, virulence factors and receptors. Recent structures of transmembrane β-barrels include that of a full length autotransporter (EstA), a bacterial heme transporter complex (HasR), a bacterial porin in complex with several ligands (PorB), and the mitochondrial voltage-dependent anion channel (VDAC) from both mouse and human. These represent only a few of the interesting structures of β-barrel membrane proteins recently elucidated. However, they demonstrate many of the advancements made within the field of transmembrane protein structure in the past few years.

Figure 1

Folding pathways for β-barrel membrane proteins in (A) Gram-negative bacteria, (B) mitochondria, and (C) chloroplasts. The folding pathways are indicated in green. While much is known about these folding pathways for bacteria and mitochondria, much less is known about chloroplasts. This panel is an adaptation from Schleiff and Soll, 2005 [10]. Currently, all that is known about the 3D structures of components involved in these pathways comes from recent work on the BAM complex. Those structures include (D) FhaC (PDB ID 2QDZ), a BamA homolog, (E) BamB (PDB ID 3Q7O), (F) BamA_POT4-5 (PDB ID 3OG5), (G) BamE (PDB ID 2KXX), and (H) BamA_POT1-4 (PDB ID 3EFC).

Figure 2

The crystal structures of the bacterial β-barrel membrane proteins (A) EstA (PDB ID 3KVN), (B) HasR (PDB ID 3CSL), and (C) PorB (3A2U). Shown in the top panel is the membrane (side) view of each structure and the middle panel represents the extracellular (top) view. For the HasR/HasA complex, HasA has been removed in the top view for clarity. For EstA, the lower panel shows the location of a C₈E₄ detergent molecule which was found in the active site of the passenger domain. The active site residues are shown in stick representation. For HasR, the lower panel shows a comparison between the two HasR mutants reported, where heme has been shuttled from HasA to HasR, likely involving residues I671 and H83. For PorB, the lower panel shows the PorB structures bound with AMP-PNP (shown in sphere representation) and sucrose (shown in stick representation) within the barrel pore.

Figure 3

(A) The crystal structure of VDAC (PDB ID 3EMN). The parallel β-strands β1 and β19 are highlighted in magenta. The N-terminal helix is shown in red. Left: side-on view of VDAC in ribbon format, middle: view down the VDAC barrel in ribbon format, right: view down the VDAC barrel as a space-filling model. (B) Homology model of Tom40 in ribbon format. Coloring for β-strands β1 and β19 and the N-terminal α-helix is as in (A). Left: side-on view of the Tom40 homology model, right: view down the Tom40 homology model barrel. The homology model for Tom40 [48] was kindly provided by Kornelius Zeth.