A self-consistent field analysis of the neurofilament brush with amino-acid resolution

¹ Wageningen University

^* To whom correspondence should be addressed. E-mail: frans.leermakers{at}wur.nl.

Submitted on September 15, 2006
Revised on November 12, 2006
Accepted on 3 January 2007

	Abstract

Using the numerical model of Scheutjens and Fleer we investigated, on a self-consistent field level, the equilibrium structure of the neurofilament brush formed by the projection domains of NF-H, NF-M and NF-L proteins. Although the actual AA sequences in the projection domains are coarse grained, the different (realistic) solubilities of AA residues and the specific distribution of its intrinsic charges inside the arms of the NF proteins, are taken explicitly into account. We collect strong evidence that the electrostatic interactions are a dominant force that controls the NF brush structure. There exists a remarkable spatial separation of the H, M and L tails. In a dephosphorylated NF we found confined and flower-like conformations for the H and M projection domains, respectively. We demonstrate that the ionization of KSP repeats in NF proteins triggers a conformational transition in the H tail that leads to the expulsion of its terminal (KEP) domain to the periphery of the NF brush. We argue that the phosphorylation of the NF proteins in axons can both increase the interfilament distance and stabilizes cross-bridges between neurofilaments.

Key Words: axonal caliber, conformation of projection domains, cross-bridges, neurofilament, polymer brush, self-consistent field theory

This article has been cited by other articles:

				J. B. Jones and C. R. Safinya Interplay between Liquid Crystalline and Isotropic Gels in Self-Assembled Neurofilament Networks Biophys. J., July 15, 2008; 95(2): 823 - 835. [Abstract] [Full Text] [PDF]

				E. B. Zhulina and F. A. M. Leermakers Effect of the Ionic Strength and pH on the Equilibrium Structure of a Neurofilament Brush Biophys. J., September 1, 2007; 93(5): 1452 - 1463. [Abstract] [Full Text] [PDF]