Since the recent availability of high sensitivity field-cycling relaxometers, it has become possible to measure the protein proton relaxation in millimolar protein solutions as a function of magnetic field. In principle, this provides direct access to the so-called spectral density function of protein protons and, hence, to a full set of dynamic parameters. Understanding the dynamic behavior of biological molecules is increasingly appreciated as crucial to understanding their function. However, theoretical tools to analyze the collective relaxation behavior of protons in solute macromolecules over a wide range of magnetic fields are lacking. A complete relaxation matrix analysis of such behavior is described here. This analysis provides excellent predictions of the experimental proton magnetization decays/recoveriessmeasured to an unprecedented level of accuracy by a last-generation fast field-cycling relaxometersof two different globular proteins, hen egg white lysozyme and human serum albumin. The new experimentally validated theoretical model is then used to extract dynamic information on these systems. A “collective” order parameter SC2, different from, but complementary to, that commonly extracted from heteronuclear relaxation measurements at high field, is defined and measured. An accurate estimate of the rotational correlation time is obtained: in the case of lysozyme it agrees very well with theoretical predictions; in the case of serum albumin it provides evidence for aggregation at millimolar concentration.

Collective relaxation of protein protons at very low magnetic field: a new window on protein dynamics and aggregation / LUCHINAT C; G. PARIGI. - In: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. - ISSN 0002-7863. - STAMPA. - 129:(2007), pp. 1055-1064. [10.1021/ja0633417]

Collective relaxation of protein protons at very low magnetic field: a new window on protein dynamics and aggregation

LUCHINAT, CLAUDIO;PARIGI, GIACOMO
2007

Abstract

Since the recent availability of high sensitivity field-cycling relaxometers, it has become possible to measure the protein proton relaxation in millimolar protein solutions as a function of magnetic field. In principle, this provides direct access to the so-called spectral density function of protein protons and, hence, to a full set of dynamic parameters. Understanding the dynamic behavior of biological molecules is increasingly appreciated as crucial to understanding their function. However, theoretical tools to analyze the collective relaxation behavior of protons in solute macromolecules over a wide range of magnetic fields are lacking. A complete relaxation matrix analysis of such behavior is described here. This analysis provides excellent predictions of the experimental proton magnetization decays/recoveriessmeasured to an unprecedented level of accuracy by a last-generation fast field-cycling relaxometersof two different globular proteins, hen egg white lysozyme and human serum albumin. The new experimentally validated theoretical model is then used to extract dynamic information on these systems. A “collective” order parameter SC2, different from, but complementary to, that commonly extracted from heteronuclear relaxation measurements at high field, is defined and measured. An accurate estimate of the rotational correlation time is obtained: in the case of lysozyme it agrees very well with theoretical predictions; in the case of serum albumin it provides evidence for aggregation at millimolar concentration.
2007
129
1055
1064
LUCHINAT C; G. PARIGI
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/309704
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