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Model-free extraction of spin label position distributions from pseudocontact shift data

Model-free extraction of spin label position distributions from pseudocontact shift data
Model-free extraction of spin label position distributions from pseudocontact shift data
A significant problem with paramagnetic tags attached to proteins and nucleic acids is their conformational mobility. Each tag is statistically distributed within a volume between 5 and 10 Angstroms across; structural biology conclusions from NMR and EPR work are necessarily diluted by this uncertainty. The problem is solved in electron spin resonance, but remains open in the other major branch of paramagnetic resonance – pseudocontact shift (PCS) NMR spectroscopy, where structural biologists have so far been reluctantly using the point paramagnetic centre approximation. Here we describe a new method for extracting probability densities of lanthanide tags from PCS data. The method relies on Tikhonov-regularised 3D reconstruction and opens a new window into biomolecular structure and dynamics because it explores a very different range of conditions from those accessible to double electron resonance work on paramagnetic tags: a room-temperature solution rather than a glass at cryogenic temperatures. The method is illustrated using four different Tm3+ DOTA-M8 tagged mutants of human carbonic anhydrase II; the results are in good agreement with rotamer library and DEER data. The wealth of high-quality pseudocontact shift data accumulated by the biological magnetic resonance community over the last 30 years, and so far only processed using point models, could now become a major source of useful information on conformational distributions of paramagnetic tags in biomolecules.
1478-6524
2751-2757
Suturina, Elizaveta
24dd007d-949a-4852-99d1-ea42b00103ef
Häussinger, Daniel
5e90e1cc-8447-42ea-9e29-35f41883c030
Zimmermann, Kaspar
3d163ef4-4951-441d-8962-9afd0082ff3c
Garbuio, Luca
583652cb-7fd7-413c-90e2-5cae54865e15
Yulikov, Maxim
e66424b5-61ef-4d7f-87e1-cf440829ff37
Jeschke, Gunnar
cee7d355-19d4-4984-9278-72997819fc0d
Kuprov, Ilya
bb07f28a-5038-4524-8146-e3fc8344c065
Suturina, Elizaveta
24dd007d-949a-4852-99d1-ea42b00103ef
Häussinger, Daniel
5e90e1cc-8447-42ea-9e29-35f41883c030
Zimmermann, Kaspar
3d163ef4-4951-441d-8962-9afd0082ff3c
Garbuio, Luca
583652cb-7fd7-413c-90e2-5cae54865e15
Yulikov, Maxim
e66424b5-61ef-4d7f-87e1-cf440829ff37
Jeschke, Gunnar
cee7d355-19d4-4984-9278-72997819fc0d
Kuprov, Ilya
bb07f28a-5038-4524-8146-e3fc8344c065

Suturina, Elizaveta, Häussinger, Daniel, Zimmermann, Kaspar, Garbuio, Luca, Yulikov, Maxim, Jeschke, Gunnar and Kuprov, Ilya (2017) Model-free extraction of spin label position distributions from pseudocontact shift data. Chemical Science, 8 (4), 2751-2757. (doi:10.1039/C6SC03736D).

Record type: Article

Abstract

A significant problem with paramagnetic tags attached to proteins and nucleic acids is their conformational mobility. Each tag is statistically distributed within a volume between 5 and 10 Angstroms across; structural biology conclusions from NMR and EPR work are necessarily diluted by this uncertainty. The problem is solved in electron spin resonance, but remains open in the other major branch of paramagnetic resonance – pseudocontact shift (PCS) NMR spectroscopy, where structural biologists have so far been reluctantly using the point paramagnetic centre approximation. Here we describe a new method for extracting probability densities of lanthanide tags from PCS data. The method relies on Tikhonov-regularised 3D reconstruction and opens a new window into biomolecular structure and dynamics because it explores a very different range of conditions from those accessible to double electron resonance work on paramagnetic tags: a room-temperature solution rather than a glass at cryogenic temperatures. The method is illustrated using four different Tm3+ DOTA-M8 tagged mutants of human carbonic anhydrase II; the results are in good agreement with rotamer library and DEER data. The wealth of high-quality pseudocontact shift data accumulated by the biological magnetic resonance community over the last 30 years, and so far only processed using point models, could now become a major source of useful information on conformational distributions of paramagnetic tags in biomolecules.

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Accepted/In Press date: 18 January 2017
e-pub ahead of print date: 20 January 2017
Published date: 1 April 2017
Organisations: Faculty of Natural and Environmental Sciences

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Local EPrints ID: 405018
URI: http://eprints.soton.ac.uk/id/eprint/405018
ISSN: 1478-6524
PURE UUID: c87cd194-353e-48de-98b2-faae30846c6a
ORCID for Ilya Kuprov: ORCID iD orcid.org/0000-0003-0430-2682

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Date deposited: 26 Jan 2017 09:39
Last modified: 16 Mar 2024 04:11

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Contributors

Author: Elizaveta Suturina
Author: Daniel Häussinger
Author: Kaspar Zimmermann
Author: Luca Garbuio
Author: Maxim Yulikov
Author: Gunnar Jeschke
Author: Ilya Kuprov ORCID iD

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