High‐Resolution NMR Determination of the Dynamic Structure of Membrane Proteins

Jaremko, Mariusz; Jaremko, Łukasz; Villinger, Saskia; Schmidt, Christian; Griesinger, Christian; Becker, Stefan; Zweckstetter, Markus

doi:10.1002/anie.201602639

Cited by 28 publications

(38 citation statements)

References 22 publications

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“…All of these show strong correlations with water, and no cross‐peak with lipids. This is fully in accordance with the known 19‐stranded beta barrel structure of the channel determined in detergent micelles, as well as the placement of the helix within the large water‐filled pore in crystals and in micelles ,,. In total, 53 correlations with water and 42 with lipids can be observed, however only approximately 19 water correlations and 17 lipid correlations can be assigned with certainty due to extensive signal overlap in the HN plane.…”

Section: Resultsmentioning

confidence: 99%

“…Figure shows water‐ and lipid‐protein correlations mapped onto the OmpW homology model of AlkL, generated with the swissmodel server and the solution NMR structure of hVDAC . For the residue mapping we combined information obtained from the well‐resolved HhnCANH and the high‐sensitivity HhNH experiments and used contacts from both spectra.…”

Section: Resultsmentioning

confidence: 99%

“…(Figure S1) Despite the reduced sensitivity, the clear advantage of the 4D spectrum is that assignments are almost completely unambiguous, due to the resolution afforded by 3 spectral dimensions, 13 CA, 15 N, and 1 H. Figure 6 shows water-and lipid-protein correlations mapped onto the OmpW homology model of AlkL, generated with the swissmodel server [52] and the solution NMR structure of hVDAC. [51] For the residue mapping we combined information obtained from the well-resolved HhnCANH and the highsensitivity HhNH experiments and used contacts from both spectra. Homologs of AlkL [53][54][55][56] are composed of a transmembrane beta barrel, with long extracellular loops that are either flexible, or form a structured beta barrel extension, depending on the sample conditions, and the homolog.…”

Section: Methodsmentioning

confidence: 99%

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Probing Membrane Protein Insertion into Lipid Bilayers by Solid‐State NMR

et al. 2018

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Determination of the environment surrounding a protein is often key to understanding its function and can also be used to infer the structural properties of the protein. By using proton‐detected solid‐state NMR, we show that reduced spin diffusion within the protein under conditions of fast magic‐angle spinning, high magnetic field, and sample deuteration allows the efficient measurement of site‐specific exposure to mobile water and lipids. We demonstrate this site specificity on two membrane proteins, the human voltage dependent anion channel, and the alkane transporter AlkL from Pseudomonas putida. Transfer from lipids is observed selectively in the membrane spanning region, and an average lipid‐protein transfer rate of 6 s−1 was determined for residues protected from exchange. Transfer within the protein, as tracked in the 15N‐1H 2D plane, was estimated from initial rates and found to be in a similar range of about 8 to 15 s−1 for several resolved residues, explaining the site specificity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Probing Membrane Protein Insertion into Lipid Bilayers by Solid‐State NMR

et al. 2018

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“…The protein data bank (PDB) structures of the outer mitochondrial voltage dependent anion channel VDAC-1 [31,32], the archaeal phototaxis receptor sensory rhodopsin II pSRII [33], and the bacterial inner membrane protein DsbB [34], illustrate the range of structural complexity that can be elucidated in atomic detail by solution NMR (Fig. 1).…”

Section: Solution Nmr Of Membrane Proteins In Detergentsmentioning

confidence: 99%

Applications of NMR to membrane proteins

Opella

Marassi

2017

Archives of Biochemistry and Biophysics

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Membrane proteins present a challenge for structural biology. In this article, we review some of the recent developments that advance the application of NMR to membrane proteins, with emphasis on structural studies in detergent-free, lipid bilayer samples that resemble the native environment. NMR spectroscopy is not only ideally suited for structure determination of membrane proteins in hydrated lipid bilayer membranes, but also highly complementary to the other principal techniques based on X-ray and electron diffraction. Recent advances in NMR instrumentation, spectroscopic methods, computational methods, and sample preparations are driving exciting new efforts in membrane protein structural biology.

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“…The molecular mechanisms of VDAC functions are unquestionably related to its three dimensional structure and conformational changes. In 2008, three atomic level structures of the mammalian VDAC isoform 1 were reported (Bayrhuber et al, 2008;Hiller et al, 2008;Ujwal et al, 2008) and others followed more recently (Choudhary et al, 2014;Hosaka et al, 2017;Jaremko et al, 2016;Schredelseker et al, 2014). In all these structures, VDAC adopts a unique β-barrel fold composed of 19 β-strands and a N-terminal α-helix leaning onto the inner barrel wall about half way along the pore (Fig.…”

Section: Introductionmentioning

confidence: 99%

Lipid composition and salt concentration as regulatory factors of the anion selectivity of VDAC studied by coarse-grained molecular dynamics simulations

Liefferinge

Krammer

Sengupta

et al. 2019

Chemistry and Physics of Lipids

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The voltage-dependent anion channel (VDAC) is a mitochondrial outer membrane protein whose fundamental function is to facilitate and regulate the flow of metabolites between the cytosol and the mitochondrial intermembrane space. Using coarse-grained molecular dynamics simulations, we investigated the dependence of VDAC selectivity towards small inorganic anions on two factors: the ionic strength and the lipid composition. In agreement with experimental data we found that VDAC becomes less anion selective with increasing salt concentration due to the screening of a few basic residues that point into the pore lumen. The molecular dynamics simulations provide insight into the regulation mechanism of VDAC selectivity by the composition in the lipid membrane and suggest that the ion distribution is differently modulated by POPE compared to the POPC bilayer. This occurs through the more persistent interactions of acidic residues located at both rims of the β-barrel with head groups of POPE which in turn impact the electrostatic potential and thereby the selectivity of the pore. This mechanism occurs not only in POPE single component membranes but also in a mixed POPE/POPC bilayer by an enrichment of POPE over POPC lipids on the surface of VDAC. Thus we show here that computationally-inexpensive coarse-grained simulations are able to capture, in a semi-quantitative way, essential features of VDAC anion selectivity and could pave the way toward a molecular level understanding of metabolite transport in natural membranes.

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High‐Resolution NMR Determination of the Dynamic Structure of Membrane Proteins

Cited by 28 publications

References 22 publications

Probing Membrane Protein Insertion into Lipid Bilayers by Solid‐State NMR

Probing Membrane Protein Insertion into Lipid Bilayers by Solid‐State NMR

Applications of NMR to membrane proteins

Lipid composition and salt concentration as regulatory factors of the anion selectivity of VDAC studied by coarse-grained molecular dynamics simulations

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