Towards Understanding Protein Disorder In-Cell
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Investigating the activity and structure of cellular biochemical machinery at atomic resolution has been a point of paramount significance for understanding health and disease over the decades. The underlying molecular mechanisms are primarily studied in vitro. Nuclear magnetic resonance (NMR) is a technique that allows to look into cells and study proteins and other constituents, thanks to careful experimental design and technological advances (spectrometer sensitivity and pulse sequence design). Here we outline current applications of the technique and propose a realistic future for the field.
KeywordsIn-cell NMR Isotopic labeling Cell types Cell extracts
Cesyen Cedeño and Hadas Raveh-Amit were fellows in the IDPbyNMR Marie Curie project of the European Commission, 7th Framework Programme (contract no. 264257), and this work has been partially supported by this project. Peter Tompa acknowledges the Research Foundation Flanders (FWO) Odysseus grant G.0029.12.
- Burz DS, Shekhtman A (2010) The STINT-NMR method for studying in-cell protein-protein interactions. Curr Protoc Protein Sci Chapter 17: Unit 17.11. doi:10.1002/0471140864.ps1711s61Google Scholar
- Croke RL, Sallum CO, Watson E et al (2008) Hydrogen exchange of monomeric α-synuclein shows unfolded structure persists at physiological temperature and is independent of molecular crowding in Escherichia coli. Protein Sci 17:1434–1445. doi:10.1110/ps.033803.107PubMedCentralCrossRefPubMedGoogle Scholar
- Li C, Charlton LM, Lakkavaram A et al (2008) Differential dynamical effects of macromolecular crowding on an intrinsically disordered protein and a globular protein: implications for in-cell NMR spectroscopy. J Am Chem Soc 130:6310–6311. doi:10.1021/ja801020zPubMedCentralCrossRefPubMedGoogle Scholar
- Xue B, Oldfield CJ, Van Y et al (2012) Protein intrinsic disorder and induced pluripotent stem cells. Mol Biosyst 8:134–150. doi:10.1039/c1mb05163fGoogle Scholar