Membrane protein dynamics and detergent interactions within a crystal: A simulation study of OmpA

Bond, Peter J.; Faraldo‐Gómez, José D.; Deol, Sundeep S.; Sansom, Mark S. P.

doi:10.1073/pnas.0600398103

Cited by 37 publications

(26 citation statements)

References 49 publications

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“…Simulated B-factors were calculated from the trajectories for the template structures as described previously (28), averaged for each system, and compared with the experimental B-factors reported for the x-ray structures (r ϭ 0.68 for A2, r ϭ 0.76 for A3G-CD; Fig. S5), suggesting the dynamics of the structure to be well captured by our MD simulation (29). Taken together, these results suggest that both models of A3C are valid from a structural point of view and thus useful to deduce further hypotheses.…”

Section: Resultsmentioning

confidence: 94%

Model structure of APOBEC3C reveals a binding pocket modulating ribonucleic acid interaction required for encapsidation

Stauch

Hofmann

Perković

et al. 2009

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

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Human APOBEC3 (A3) proteins form part of the intrinsic immunity to retroviruses. Carrying 1 or 2 copies of a cytidine deaminase motif, A3s act by deamination of retroviral genomes during reverse transcription. HIV-1 overcomes this inhibition by the Vif protein, which prevents incorporation of A3 into virions. In this study we modeled and probed the structure of APOBEC3C (A3C), a singledomain A3 with strong antilentiviral activity. The 3-dimensional protein model was used to predict the effect of mutations on antiviral activity, which was tested in a ⌬vif simian immunodeficiency virus (SIV) reporter virus assay. We found that A3C activity requires protein dimerization for antiviral activity against SIV. Furthermore, by using a structure-based algorithm for automated pocket extraction, we detected a putative substrate binding pocket of A3C distal from the zinc-coordinating deaminase motif. Mutations in this region diminished antiviral activity by excluding A3C from virions. We found evidence that the small 5.8S RNA specifically binds to this locus and mediates incorporation of A3C into virus particles.Bioinformatics ͉ immunodeficiency ͉ protein structure ͉ proteinϪprotein interaction ͉ retrovirus

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Section: Resultsmentioning

confidence: 94%

Model structure of APOBEC3C reveals a binding pocket modulating ribonucleic acid interaction required for encapsidation

Stauch

Hofmann

Perković

et al. 2009

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

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“…but rather reveals relaxation of the protein in its changed environment [29,30]. We also analysed the root mean square fluctuations (RMSFs) of each Ca atom from its mean position as a function of residue number (see Supplementary Data, Figure S2, online version only).…”

Section: Overall Protein Conformation: Drift and Fluctuationsmentioning

confidence: 99%

Conformational dynamics of the mitochondrial ADP/ATP carrier: a simulation study

Johnston

Khalid

Sansom

2008

Molecular Membrane Biology

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The mitochondrial ADP/ATP carrier is a six helix bundle membrane transport protein, which couples the exit of ATP from the mitochondrial matrix to the entry of ADP. Extended (4x20 ns) molecular dynamics simulations of the carrier, in the presence and absence of bound inhibitor (carboxyatractyloside), have been used to explore the conformational dynamics of the protein in a lipid bilayer environment, in the presence and absence of the carboxyatractyloside inhibitor. The dynamic flexibility (measured as conformational drift and fluctuations) of the protein is reduced in the presence of bound inhibitor. Proline residues in transmembrane helices H1, H3 and H5 appear to form dynamic hinges. Fluctuations in inter-helix salt bridges are also observed over the time course of the simulations. Inhibitor-protein and lipid-protein interactions have been characterised in some detail. Overall, the simulations support a transport mechanism in which flexibility about the proline hinges enables a transition between a 'closed' and an 'open' pore-like state of the carrier protein.

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“…MD simulation also offers the possibility to compare the dynamics of a membrane protein in the experimental environment, i.e. in protein/detergent co-crystals used for X-ray diffraction experiments or in protein-micelle aggregates used for solution NMR experiments, to its dynamics when embedded in a lipid bilayer, as has been done for OmpA from Escherichia coli (Bond and Sansom 2003).…”

Section: Introductionmentioning

confidence: 99%

Membrane protein dynamics in different environments: simulation study of the outer membrane protein X in a lipid bilayer and in a micelle

et al. 2010

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The bacterial outer membrane protein OmpX from Escherichia coli has been investigated by molecular dynamics simulations when embedded in a phospholipid bilayer and as a protein-micelle aggregate. The resulting simulation trajectories were analysed in terms of structural and dynamic properties of the membrane protein. In agreement with experimental observations, highest relative stability was found for the β-barrel region that is embedded in the lipophilic phase, whereas an extracellular protruding β-sheet, which is a unique structural feature of OmpX that supposedly plays an important role in cell adhesion and invasion, shows larger structure fluctuations. Additionally, we investigated water permeation into the core of the β-barrel protein, which contains a tight salt-bridge and hydrogen-bond network, so that extensive water flux is unlikely. Differences between the bilayer and the micellar system were observed in the length of the barrel and its position inside the lipid environment, and in the protein interactions with the hydrophilic part of the lipids near the lipid/water interface. Those variations suggest that micelles and other detergent environments might not offer a wholly membrane-like milieu to promote adoption of the physiological conformational state by OmpX.

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Membrane protein dynamics and detergent interactions within a crystal: A simulation study of OmpA

Cited by 37 publications

References 49 publications

Model structure of APOBEC3C reveals a binding pocket modulating ribonucleic acid interaction required for encapsidation

Model structure of APOBEC3C reveals a binding pocket modulating ribonucleic acid interaction required for encapsidation

Conformational dynamics of the mitochondrial ADP/ATP carrier: a simulation study

Membrane protein dynamics in different environments: simulation study of the outer membrane protein X in a lipid bilayer and in a micelle

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