Temperature-dependent oligomerization in M-crystallin: lead or lag toward cataract, an NMR perspective

Barnwal, Ravi P. ; Manjula Devi, K. ; Agarwal, Geetika ; Sharma, Yogendra ; Chary, Kandala V. R. (2011) Temperature-dependent oligomerization in M-crystallin: lead or lag toward cataract, an NMR perspective Proteins: Structure, Function, and Bioinformatics, 79 (9). pp. 569-580. ISSN 0887-3585

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Official URL: http://onlinelibrary.wiley.com/doi/10.1002/prot.22...

Related URL: http://dx.doi.org/10.1002/prot.22905

Abstract

The oligomerization and/or aggregation of proteins is of critical importance in a wide variety of biomedical situations, ranging from abnormal disease states like Alzheimer's and Parkinson's disease to the production of inclusion bodies, stability, and delivery of protein drugs. In the case of eye-lens proteins, oligomerization is implicated in cataract formation. In the present study, we have investigated the temperature driven oligomerization of M-crystallin, a close homologue of eye-lens proteins, using NMR spectroscopy and dynamic-light scattering (DLS). The NMR data primarily included R1, R2 relaxation rates and nOes of the backbone amide groups recorded at three different temperatures, 25, 20, and 15°C. The major outcome of the study is the two fold increase in the overall tumbling time (τc) of M-crystallin on lowering the temperature from 25 to 15°C. An extrapolation of τc to a further lower temperature (5°C) may lead to a τc of ~19 ns that would correspond to a τc value of a tetrameric M-crystallin. These results also validate the observed changes in the hydrodynamic radius of M-crystallin, determined using DLS data. Further, the temperature-dependent protein dynamics of M-crystallin reveal considerable variation at/near the Ca2+-binding sites. A concerted analysis of the temperature dependent relaxation parameters and DLS data reveals that the self-association of the protein is not only a monomer-dimer equilibrium, but also goes to tetramers or other multimeric states. These higher states may co-exist in fast exchange with the monomeric and dimeric M-crystallin at milli-molar to sub-millimolar concentrations and at lower temperature.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:Eye Lens; Crystallin; Cataract; NMR Dynamics; Dynamic Light Scattering (DLS); Oligomerization
ID Code:50887
Deposited On:27 Jul 2011 13:29
Last Modified:27 Jul 2011 13:29

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