Solid‐state NMR for the analysis of high‐affinity ligand/receptor interactions

Williamson, Philip T. F.

doi:10.1002/cmr.a.20140

Cited by 19 publications

(9 citation statements)

References 153 publications

(196 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oriented solid-state NMR, with in particular the PISEMA experiment [14], is another powerful tool to characterize the immersion and tilt angle of a membrane protein inside the bilayer [15–18]. Magic-angle spinning (MAS) NMR offers the possibility to design an unlimited number of experiments [19,20]. The location of membrane-embedded systems can be assessed by measuring the exposure of the protein to paramagnetic labels [21,22].…”

Section: Introductionmentioning

confidence: 99%

Cardiolipin interaction with subunit c of ATP synthase: Solid-state NMR characterization

Laage

Tao

McDermott

2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

The interaction of lipids with subunit c from F1F0 ATP synthase is studied by biophysical methods. Subunit c from both Escherichia coli and Streptococcus pneumoniae interacts and copurifies with cardiolipin. Solid state NMR data on oligomeric rings of F0 show that the cardiolipin interacts with the c subunit in membrane bilayers. These studies offer strong support for the hypothesis that F0 has specific interactions with cardiolipin.

show abstract

Section: Introductionmentioning

confidence: 99%

Cardiolipin interaction with subunit c of ATP synthase: Solid-state NMR characterization

Laage

Tao

McDermott

2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

show abstract

“…MAS solid-state NMR is also very useful for elucidating the atomicresolution structures, molecular conformations, positions and orientations of ligands and drug compounds in the binding sites of membrane proteins from measurement of accurate interatomic distances and torsion angles (Cady et al, 2010;Edwards et al, 2010;Lakatos et al, 2012;Lopez et al, 2008;Middleton et al, 2011;Patching et al, 2008Patching et al, , 2013Whittaker et al, 2015;Williamson et al, 2007). Such measurements can contribute important information for the design and discovery of drugs involving membrane-embedded targets (Ding et al, 2013a;Tapaneeyakorn et al, 2011;Watts, 2005;Williamson, 2009).…”

Section: Mas Solid-state Nmrmentioning

confidence: 99%

Solid-state NMR structures of integral membrane proteins

Patching¹

2015

Molecular Membrane Biology

View full text Add to dashboard Cite

Solid-state NMR is unique for its ability to obtain three-dimensional structures and to measure atomic-resolution structural and dynamic information for membrane proteins in native lipid bilayers. An increasing number and complexity of integral membrane protein structures have been determined by solid-state NMR using two main methods. Oriented sample solid-state NMR uses macroscopically aligned lipid bilayers to obtain orientational restraints that define secondary structure and global fold of embedded peptides and proteins and their orientation and topology in lipid bilayers. Magic angle spinning (MAS) solid-state NMR uses unoriented rapidly spinning samples to obtain distance and torsion angle restraints that define tertiary structure and helix packing arrangements. Details of all current protein structures are described, highlighting developments in experimental strategy and other technological advancements. Some structures originate from combining solid- and solution-state NMR information and some have used solid-state NMR to refine X-ray crystal structures. Solid-state NMR has also validated the structures of proteins determined in different membrane mimetics by solution-state NMR and X-ray crystallography and is therefore complementary to other structural biology techniques. By continuing efforts in identifying membrane protein targets and developing expression, isotope labelling and sample preparation strategies, probe technology, NMR experiments, calculation and modelling methods and combination with other techniques, it should be feasible to determine the structures of many more membrane proteins of biological and biomedical importance using solid-state NMR. This will provide three-dimensional structures and atomic-resolution structural information for characterising ligand and drug interactions, dynamics and molecular mechanisms of membrane proteins under physiological lipid bilayer conditions.

show abstract

“…Solid-state NMR is amenable to a wider range of sample types for membrane proteins; they may be used expressed in their native membranes, purified and reconstituted in detergents or lipids, or in a crystalline or lyophilized state; (see work by Lorch et al 2005, Watts 2007, De Angelis and Opella 2007, Williamson 2009and Tapaneeyakorn et al 2011 for descriptions of sample preparation strategies for solidstate NMR on membrane proteins).…”

Section: Purification and Reconstitutionmentioning

confidence: 99%

NMR structures of polytopic integral membrane proteins

Patching

2011

Molecular Membrane Biology

View full text Add to dashboard Cite

Membrane proteins represent up to 30% of the proteins in all organisms, they are involved in many biological processes and are the molecular targets for around 50% of validated drugs. Despite this, membrane proteins represent less than 1% of all high-resolution protein structures due to various challenges associated with applying the main biophysical techniques used for protein structure determination. Recent years have seen an explosion in the number of high-resolution structures of membrane proteins determined by NMR spectroscopy, especially for those with multiple transmembrane-spanning segments. This is a review of the structures of polytopic integral membrane proteins determined by NMR spectroscopy up to the end of the year 2010, which includes both β-barrel and α-helical proteins from a number of different organisms and with a range in types of function. It also considers the challenges associated with performing structural studies by NMR spectroscopy on membrane proteins and how some of these have been overcome, along with its exciting potential for contributing new knowledge about the molecular mechanisms of membrane proteins, their roles in human disease, and for assisting drug design.

show abstract

Solid‐state NMR for the analysis of high‐affinity ligand/receptor interactions

Cited by 19 publications

References 153 publications

Cardiolipin interaction with subunit c of ATP synthase: Solid-state NMR characterization

Cardiolipin interaction with subunit c of ATP synthase: Solid-state NMR characterization

Solid-state NMR structures of integral membrane proteins

NMR structures of polytopic integral membrane proteins

Contact Info

Product

Resources

About