Sequential acquisition of multi-dimensional heteronuclear chemical shift correlation spectra with 1H detection

Bellstedt, Peter; Ihle, Yvonne; Wiedemann, Christoph; Kirschstein, Anika; Herbst, Christian T.; Görlach, Matthias; Ramachandran, Ramadurai

doi:10.1038/srep04490

Cited by 15 publications

(12 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Protein intramolecular distance restraints for membrane-bound CD 260-290 were derived from cross-peaks with a simultaneous 15 N and 13 C-NOESY-HSQC (τ NOE = 120 ms) experiments 55 , 56 on a 15 N/ 13 C-labeled sample. Peak analysis of the NOESY spectra was generated by interactive peak picking with the program Sparky 50 .…”

Section: Methodsmentioning

confidence: 99%

PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain

Wen

Cao

et al. 2021

Nat Commun

View full text Add to dashboard Cite

The cytoplasmic domain of PD-L1 (PD-L1-CD) regulates PD-L1 degradation and stability through various mechanism, making it an attractive target for blocking PD-L1-related cancer signaling. Here, by using NMR and biochemical techniques we find that the membrane association of PD-L1-CD is mediated by electrostatic interactions between acidic phospholipids and basic residues in the N-terminal region. The absence of the acidic phospholipids and replacement of the basic residues with acidic residues abolish the membrane association. Moreover, the basic-to-acidic mutations also decrease the cellular abundance of PD-L1, implicating that the electrostatic interaction with the plasma membrane mediates the cellular levels of PD-L1. Interestingly, distinct from its reported function as an activator of AMPK in tumor cells, the type 2 diabetes drug metformin enhances the membrane dissociation of PD-L1-CD by disrupting the electrostatic interaction, thereby decreasing the cellular abundance of PD-L1. Collectively, our study reveals an unusual regulatory mechanism that controls the PD-L1 level in tumor cells, suggesting an alternative strategy to improve the efficacy of PD-L1-related immunotherapies.

show abstract

Section: Methodsmentioning

confidence: 99%

PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain

Wen

Cao

et al. 2021

Nat Commun

View full text Add to dashboard Cite

show abstract

“…The extension of these techniques to higher-dimensional experiments is an obvious area for future development. Although time-shared 3D and 4D sequences have long been used in biomolecular NMR [162][163][164] , there has been much less work on sequential and multi-nuclear acquisition experiments 82,83,102 .…”

Section: Discussionmentioning

confidence: 99%

Parallel nuclear magnetic resonance spectroscopy

Kupče

Frydman

Webb

et al. 2021

Nat Rev Methods Primers

View full text Add to dashboard Cite

Nuclear Magnetic Resonance (NMR) spectroscopy is a principal analytical technique used for the structure elucidation of molecules. This Primer covers different approaches to accelerate data acquisition and increase sensitivity of NMR measurements through parallelisation, enabled by hardware design and/or pulse sequence development. Starting with hardware-based methods, we discuss coupling multiple detectors to multiple samples so each detector/sample combination provides unique information. We then cover spatiotemporal encoding, which uses external field gradients and frequency selective manipulations to parallelize multi-dimensional acquisition and compress it into a single-shot. The parallel manipulation of different magnetisation reservoirs within a sample is then considered, yielding new, information-rich pulse schemes using either homo-or multinuclear detection. The Experimentation section describes the setup of parallel NMR techniques. Practical examples revealing improvements in speed and sensitivity offered by the parallel methods are demonstrated in the Results section. Examples of use of parallelization in small molecule analysis are discussed in the Applications section with experimental constraints addressed under the Limitation, Optimisations, and Reproducibility and Data Deposition sections. The most promising future developments are considered in the Outlook section, where the largest gains are expected to emerge once the discussed techniques are combined.

show abstract

“…Furthermore, in many cases the NOAH technique offers also better sensitivity per unit time as compared to the corresponding standalone experiments (see the Supporting Information). While sequential acquisition of 1 H detected experiments is not new [16,27,[33][34][35], it is the modularity aspect of the NOAH technique that allows design of new modules based on a variety of techniques and approaches [32] that can be combined into many different supersequences, which in turn provide more efficient means to record multiple sets of NMR spectra required for small molecule analysis and structure elucidation.…”

Section: Discussionmentioning

confidence: 99%

New NOAH modules for structure elucidation at natural isotopic abundance

Kupče

Claridge

2019

Journal of Magnetic Resonance

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

Sequential acquisition of multi-dimensional heteronuclear chemical shift correlation spectra with 1H detection

Cited by 15 publications

References 35 publications

PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain

PD-L1 degradation is regulated by electrostatic membrane association of its cytoplasmic domain

Parallel nuclear magnetic resonance spectroscopy

New NOAH modules for structure elucidation at natural isotopic abundance

Contact Info

Product

Resources

About