Gene Duplication of the Eight-stranded β-Barrel OmpX Produces a Functional Pore: A Scenario for the Evolution of Transmembrane β-Barrels

Arnold, Thomas C.; Poynor, Melissa; Nußberger, Stephan; Lupas, Andrei N.; Linke, Dirk

doi:10.1016/j.jmb.2006.12.029

Cited by 83 publications

(125 citation statements)

References 52 publications

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“…Our combined approach using data of both NMR spectroscopy and x-ray crystallography enabled the determination of the 3D structure of the first MOM protein, hVDAC1. The finding of a 19-stranded ␤-barrel is in strong contrast to evolutionary theories predicting bacterial ␤-barrels and related proteins to be formed by an ancient ␤-hairpin motif (37). The new channel architecture is likely to be a consequence of the differences in membrane environment, sorting signal and partner proteins experienced by integral membrane proteins of the outer membrane of bacteria and those of the MOM and most likely adopted by other MOM proteins.…”

Section: Dimerization Of Vdac Via a Small Hydrophobic Interfacementioning

confidence: 68%

Structure of the human voltage-dependent anion channel

Bayrhuber

Meins

Habeck

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

495

617

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The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is the most abundant protein in the mitochondrial outer membrane (MOM). VDAC is the channel known to guide the metabolic flux across the MOM and plays a key role in mitochondrially induced apoptosis. Here, we present the 3D structure of human VDAC1, which was solved conjointly by NMR spectroscopy and x-ray crystallography. Human VDAC1 (hVDAC1) adopts a ␤-barrel architecture composed of 19 ␤-strands with an ␣-helix located horizontally midway within the pore. Bioinformatic analysis indicates that this channel architecture is common to all VDAC proteins and is adopted by the general import pore TOM40 of mammals, which is also located in the MOM.T he outer membrane of mitochondria (MOM) contains three integral membrane protein families, two of which form channels as part of larger protein complexes (for review, see ref. 1). These two MOM complexes, the general import pore TOM and the SAM insertase, allow for the entire translocation and insertion of nearly all newly synthesized proteins destined to the mitochondrial organelle (2, 3). The third protein family of typically high abundance (Ϸ10,000 copies per mitochondrion) is termed voltage-dependent anion channels (VDACs), because of the voltage sensitivity of its open probability (4, 5). Together, this small number of protein families is sufficient for full communication between mitochondria with their cellular environment (1).The VDAC channel was initially described as being reminiscent of bacterial porins and primarily responsible for the exchange of chemical energy equivalents between the cytosol and the mitochondrion (4, 6). Indeed, a variety of structural features (like barrel geometry and dimension) known from the bacterial precursors are maintained (7,8). By contrast, a variety of functions have been ascribed to the VDAC isoforms among which the direct coupling of the mitochondrial matrix to the energy maintenance of the cytosol seems to be the most general function (9). The structure of VDAC is of interest because of a substantial body of evidence connecting VDAC to apoptosis. It is suggested that VDAC is a critical player in the release of apoptogenic factors from mitochondria of mammalian cells, and consequently several hypotheses describing the mechanism of mitochondria-mediated apoptosis involving VDAC have been proposed (for review, see ref. 10). Results and DiscussionStructure Determination of hVDAC1: Combining NMR Spectroscopy and X-Ray Crystallography. In a parallel structural biology approach, we set out to characterize the structure of hVDAC1, the major isoform of this channel in mammalian tissues, by a combination of NMR spectroscopy and x-ray crystallography. The idea behind this project was to gain complementary structural information to have a solid basis for future studies, e.g., analysis of protein heterocomplex formation by NMR and crystal structures as a basis for drug target design. Only information derived from both methods and the application of an iterative s...

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Section: Dimerization Of Vdac Via a Small Hydrophobic Interfacementioning

confidence: 68%

Structure of the human voltage-dependent anion channel

Bayrhuber

Meins

Habeck

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

495

617

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“…Their homologous origin has been discussed recently. 40,41 In the remaining nine clusters, the connections between domains clearly result from the presence of sequence-and structure-similar subdomain-sized fragments. For example, one large cluster contains a variety of topologically distinct DNA-binding domains with a common helix-turn-helix motif (large, mainly red cluster at the middle in Fig.…”

Section: Resultsmentioning

confidence: 99%

A galaxy of folds

et al. 2009

Self Cite

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Many protein classification systems capture homologous relationships by grouping domains into families and superfamilies on the basis of sequence similarity. Superfamilies with similar 3D structures are further grouped into folds. In the absence of discernable sequence similarity, these structural similarities were long thought to have originated independently, by convergent evolution. However, the growth of databases and advances in sequence comparison methods have led to the discovery of many distant evolutionary relationships that transcend the boundaries of superfamilies and folds. To investigate the contributions of convergent versus divergent evolution in the origin of protein folds, we clustered representative domains of known structure by their sequence similarity, treating them as point masses in a virtual 2D space which attract or repel each other depending on their pairwise sequence similarities. As expected, families in the same superfamily form tight clusters. But often, superfamilies of the same fold are linked with each other, suggesting that the entire fold evolved from an ancient prototype. Strikingly, some links connect superfamilies with different folds. They arise from modular peptide fragments of between 20 and 40 residues that co-occur in the connected folds in disparate structural contexts. These may be descendants of an ancestral pool of peptide modules that evolved as cofactors in the RNA world and from which the first folded proteins arose by amplification and recombination. Our galaxy of folds summarizes, in a single image, most known and many yet undescribed homologous relationships between protein superfamilies, providing new insights into the evolution of protein domains.

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“…Single Channel Conductance Measurements-Bilayer membranes were prepared by the painting method as described previously (25). A 1% (w/v) solution of DPhPC in 1:1 (v/v) methanol/chloroform was applied to a 150-m aperture of the septum of a Teflon cuvette separating both the cis and the trans compartment.…”

Section: Methodsmentioning

confidence: 99%