BIOPHYSICAL THEORY AND MODELING |
Dynamic Switching Mechanisms in LOV1 and LOV2 Domains of Plant Phototropins
Peter L. Freddolino 1, Markus Dittrich 1 and Klaus Schulten 2*
1 University of Illinois at Urbana-Champaign
2 University of Illinois 3143 Beckman Institute
* To whom correspondence should be addressed. E-mail: kschulte{at}ks.uiuc.edu.
Submitted on May 7, 2006
Revised on June 13, 2006
Accepted on 10 August 2006
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Abstract |
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LOV domains are the light sensitive portion of plant phototropins. They absorb light through a flavin cofactor, photochemically form a covalent bond between the chromophore and a cysteine residue in the protein, and proceed to mediate activation of an attached kinase domain. Although the photoreaction itself is now well characterized experimentally and computationally, it is still unclear how the formation of the adduct leads to kinase activation. We have performed molecular dynamics simulations on the LOV1 domain of C. reinhardtii and the LOV2 domain of A. sativa, both before and after the photoreaction, to answer this question. The extensive simulations, over 240 ns in duration, reveal significant differences in how the LOV1 and LOV2 domains respond to photoactivation. The simulations indicate that LOV1 activation is likely caused by a change in hydrogen bonding between protein and ligand which destabilizes a highly conserved salt bridge, whereas LOV2 activation seems to result from a change in the flexibility of a set of protein loops. Results of electrostatics calculations, principal component analysis, sequence alignments, and RMSD analysis corroborate the above findings.
Key Words:
dynamic switching, kinase activation, molecular dynamics, molecular switch, photoreceptor
