Nanosecond to Microsecond Protein Dynamics Probed by Magnetic Relaxation Dispersion of Buried Water Molecules
(2008) In Journal of the American Chemical Society 130(5). p.1774-1787- Abstract
- Large-scale protein conformational motions on nanosecond – microsecond time scales are important for many biological processes, but remain largely unexplored because of methodological limitations. NMR relaxation methods can access these time scales if protein tumbling is prevented, but the isotropy required for high-resolution solution NMR is then lost. However, if the immobilized protein molecules are randomly oriented, the water 2H and 17O spins relax as in a solution of freely tumbling protein molecules, with the crucial difference that they now sample motions on all time scales up to ~100 μs. In particular, the exchange rates of internal water molecules can be determined directly from the 2H or 17O magnetic relaxation dispersion (MRD)... (More)
- Large-scale protein conformational motions on nanosecond – microsecond time scales are important for many biological processes, but remain largely unexplored because of methodological limitations. NMR relaxation methods can access these time scales if protein tumbling is prevented, but the isotropy required for high-resolution solution NMR is then lost. However, if the immobilized protein molecules are randomly oriented, the water 2H and 17O spins relax as in a solution of freely tumbling protein molecules, with the crucial difference that they now sample motions on all time scales up to ~100 μs. In particular, the exchange rates of internal water molecules can be determined directly from the 2H or 17O magnetic relaxation dispersion (MRD) profile. This possibility opens up a new window for characterizing the motions of individual internal water molecules as well as the large-scale protein conformational fluctuations that govern the exchange rates of structural water molecules. We introduce and validate this new NMR method by presenting and analyzing an extensive set of 2H and 17O MRD data from cross-linked gels of two model proteins: bovine pancreatic trypsin inhibitor and ubiquitin. We determine residence times and order parameters of four internal water molecules in these proteins and show that they are quantitatively consistent with the information available from crystallography and solution MRD. We also show how slow motions of side-chains bearing labile hydrogens can be monitored by the same approach. Proteins of any size can be studied at physiological hydration levels with this method. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/937791
- author
- Persson Sunde, Erik LU and Halle, Bertil LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of the American Chemical Society
- volume
- 130
- issue
- 5
- pages
- 1774 - 1787
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- wos:000253100100052
- scopus:38949183943
- pmid:18183977
- ISSN
- 1520-5126
- DOI
- 10.1021/ja0775873
- language
- English
- LU publication?
- yes
- id
- 56bcf8a3-0876-40ed-bc8f-d425907926b8 (old id 937791)
- date added to LUP
- 2016-04-01 11:47:20
- date last changed
- 2022-04-05 05:06:28
@article{56bcf8a3-0876-40ed-bc8f-d425907926b8,
abstract = {{Large-scale protein conformational motions on nanosecond – microsecond time scales are important for many biological processes, but remain largely unexplored because of methodological limitations. NMR relaxation methods can access these time scales if protein tumbling is prevented, but the isotropy required for high-resolution solution NMR is then lost. However, if the immobilized protein molecules are randomly oriented, the water 2H and 17O spins relax as in a solution of freely tumbling protein molecules, with the crucial difference that they now sample motions on all time scales up to ~100 μs. In particular, the exchange rates of internal water molecules can be determined directly from the 2H or 17O magnetic relaxation dispersion (MRD) profile. This possibility opens up a new window for characterizing the motions of individual internal water molecules as well as the large-scale protein conformational fluctuations that govern the exchange rates of structural water molecules. We introduce and validate this new NMR method by presenting and analyzing an extensive set of 2H and 17O MRD data from cross-linked gels of two model proteins: bovine pancreatic trypsin inhibitor and ubiquitin. We determine residence times and order parameters of four internal water molecules in these proteins and show that they are quantitatively consistent with the information available from crystallography and solution MRD. We also show how slow motions of side-chains bearing labile hydrogens can be monitored by the same approach. Proteins of any size can be studied at physiological hydration levels with this method.}},
author = {{Persson Sunde, Erik and Halle, Bertil}},
issn = {{1520-5126}},
language = {{eng}},
number = {{5}},
pages = {{1774--1787}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Journal of the American Chemical Society}},
title = {{Nanosecond to Microsecond Protein Dynamics Probed by Magnetic Relaxation Dispersion of Buried Water Molecules}},
url = {{http://dx.doi.org/10.1021/ja0775873}},
doi = {{10.1021/ja0775873}},
volume = {{130}},
year = {{2008}},
}