Structures and interactions in 'bottlebrush' neurofilaments: the role of charged disordered proteins in forming hydrogel networks. (19th September 2012)

• Record Type: Journal Article
• Authors: Beck, Roy; Deek, Joanna; Safinya, Cyrus R.
• Is Part Of: Biochemical Society transactions. Volume 40:Number 5(2012)
• Page Start: 1027
• Page End: 1031
• Publication Date: 2012-09-19
• Subjects: atomic force microscopy (AFM) -- intrinsically disordered protein -- neurofilament -- polyampholyte interactions -- small-angle X-ray scattering (SAXS); Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20120101
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : NFs (neurofilaments), the major cytoskeletal constituent of myelinated axons in vertebrates, consist of three different molecular-mass subunit proteins, NF-L (low), NF-M (medium) and NF-H (high), assembled to form mature filaments with protruding intrinsically disordered C-terminal side-arms. Liquid crystal gel networks of side-arm-mediated NF assemblies play a key role in the mechanical stability of neuronal processes. Disruptions of the NF network, due to NF overaccumulation or incorrect side-arm interactions, are a hallmark of motor neuron diseases including amyotrophic lateral sclerosis. Using synchrotron small-angle X-ray scattering and various microscopy techniques, we have investigated the role of the peptide charges in the subunit side-arms on the structure and interaction of NFs. Our findings, which delineate the distinct roles of NF-M and NF-H in regulating NF interactions, shed light on possible mechanisms of disruption of optimal mechanical network properties.