Protein Structure Determination Using Long-Distance Constraints from Double-Quantum Coherence ESR:  Study of T4 Lysozyme

Borbat, Peter P.; Mchaourab, Hassane S.; Freed, Jack H.

doi:10.1021/ja020040y

Cited by 266 publications

(302 citation statements)

References 56 publications

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“…A good example concerns a large number of distance histograms between pairs of spin label that are measured by electron spin resonance (ESR) double electron electron resonance (DEER) spectroscopy. 23 Incorporating such massive amount of data in structural models is essentially infeasible, unless one adopts a restrained-ensemble simulation strategy. Future efforts will be devoted to expand and develop the computational methodology for treating ESR/DEER distance histogram.…”

Section: Discussionmentioning

confidence: 99%

On the statistical equivalence of restrained-ensemble simulations with the maximum entropy method

Roux

Weare

2013

The Journal of Chemical Physics

191

270

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An issue of general interest in computer simulations is to incorporate information from experiments into a structural model. An important caveat in pursuing this goal is to avoid corrupting the resulting model with spurious and arbitrary biases. While the problem of biasing thermodynamic ensembles can be formulated rigorously using the maximum entropy method introduced by Jaynes, the approach can be cumbersome in practical applications with the need to determine multiple unknown coefficients iteratively. A popular alternative strategy to incorporate the information from experiments is to rely on restrained-ensemble molecular dynamics simulations. However, the fundamental validity of this computational strategy remains in question. Here, it is demonstrated that the statistical distribution produced by restrained-ensemble simulations is formally consistent with the maximum entropy method of Jaynes. This clarifies the underlying conditions under which restrained-ensemble simulations will yield results that are consistent with the maximum entropy method.

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Section: Discussionmentioning

confidence: 99%

On the statistical equivalence of restrained-ensemble simulations with the maximum entropy method

Roux

Weare

2013

The Journal of Chemical Physics

191

270

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“…(15,(25)(26)(27)(28)(29). However, having extensive interface mapping data from solvent accessibility measurements permitted the determination of structural models without the need for these approaches.…”

Section: Methodsmentioning

confidence: 99%

Determination of Structural Models of the Complex between the Cytoplasmic Domain of Erythrocyte Band 3 and Ankyrin-R Repeats 13–24

Kim

Brandon

Zhou

et al. 2011

Journal of Biological Chemistry

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The adaptor protein ankyrin-R interacts via its membrane binding domain with the cytoplasmic domain of the anion exchange protein (AE1) and via its spectrin binding domain with the spectrin-based membrane skeleton in human erythrocytes. This set of interactions provides a bridge between the lipid bilayer and the membrane skeleton, thereby stabilizing the membrane. Crystal structures for the dimeric cytoplasmic domain of AE1 (cdb3) and for a 12-ankyrin repeat segment (repeats 13-24) from the membrane binding domain of ankyrin-R (AnkD34) have been reported. However, structural data on how these proteins assemble to form a stable complex have not been reported. In the current studies, site-directed spin labeling, in combination with electron paramagnetic resonance (EPR) and double electron-electron resonance, has been utilized to map the binding interfaces of the two proteins in the complex and to obtain inter-protein distance constraints. These data have been utilized to construct a family of structural models that are consistent with the full range of experimental data. These models indicate that an extensive area on the peripheral domain of cdb3 binds to ankyrin repeats 18 -20 on the top loop surface of AnkD34 primarily through hydrophobic interactions. This is a previously uncharacterized surface for binding of cdb3 to AnkD34. Because a second dimer of cdb3 is known to bind to ankyrin repeats 7-12 of the membrane binding domain of ankyrin-R, the current models have significant implications regarding the structural nature of a tetrameric form of AE1 that is hypothesized to be involved in binding to full-length ankyrin-R in the erythrocyte membrane.Human erythrocytes exhibit an unusual biconcave disc shape and remarkable plasma membrane mechanical stability and deformability, all of which are necessary for their survival in the circulatory system. It is now well established that the unusual cell shape and membrane mechanical properties are due in large part to the presence of an extensive membrane skeleton, composed primarily of the proteins spectrin and actin, that lines the inner membrane surface and to specific bridging interactions between this membrane skeleton and intrinsic membrane proteins in the lipid bilayer. The spectrin-actin skeleton associates with the membrane bilayer via two types of contacts, one involving short actin protofilaments and protein 4.1, which interact with the cytoplasmic domain of glycophorin C, and the second involving the bridging protein ankyrin-R and protein 4.2, which interact with the cytoplasmic domain of the anion exchange protein (AE1) 3 also known as band 3. Alterations in this second class of interactions often result in spherical erythrocytes with decreased cell size and increased fragility, a condition known clinically as hereditary spherocytosis. Hereditary spherocytosis is a spectrum of inherited diseases, occurring in one family out of 2,000 -3,000, which present clinically as varying degrees of hemolytic anemia resulting from hemolysis of the spherical erythrocytes ...

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“…Within the past decade, distance distribution measurements for pairs of spin labels with pulsed dipolar spectroscopy methods have been performed for a number of proteins with known structures [60,100,[128][129][130][131][132][133][134][135][136][137][138][139][140]. From these studies, a few were selected where mean distances were given and where the duration of the dipolar evolution was sufficient [21] for these mean distances to be reliable.…”

Section: Effects On Measurements Of Distance Distributionsmentioning

confidence: 99%

Conformational dynamics and distribution of nitroxide spin labels

Jeschke

2013

Progress in Nuclear Magnetic Resonance Spectroscopy

137

115

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Long-range distance measurements based on paramagnetic relaxation enhancement (PRE) in NMR, quantification of surface water dynamics near biomacromolecules by Overhauser dynamic nuclear polarization (DNP) and sensitivity enhancement by solid-state DNP all depend on introducing paramagnetic species into an otherwise diamagnetic NMR sample. The species can be introduced by site-directed spin labeling, which offers precise control for positioning the label in the sequence of a biopolymer. However, internal flexibility of the spin label gives rise to dynamic processes that potentially influence PRE and DNP behavior and leads to a spatial distribution of the electron spin even in solid samples. Internal dynamics of spin labels and their static conformational distributions have been studied mainly by electron paramagnetic resonance spectroscopy and molecular dynamics simulations, with a large body of results for the most widely applied methanethiosulfonate spin label MTSL. These results are critically discussed in a unifying picture based on rotameric states of the group that carries the spin label. Deficiencies in our current understanding of dynamics and conformations of spin labeled groups and of their influence on NMR observables are highlighted and directions for further research suggested.

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Protein Structure Determination Using Long-Distance Constraints from Double-Quantum Coherence ESR: Study of T4 Lysozyme

Cited by 266 publications

References 56 publications

On the statistical equivalence of restrained-ensemble simulations with the maximum entropy method

On the statistical equivalence of restrained-ensemble simulations with the maximum entropy method

Determination of Structural Models of the Complex between the Cytoplasmic Domain of Erythrocyte Band 3 and Ankyrin-R Repeats 13–24

Conformational dynamics and distribution of nitroxide spin labels

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