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Biophys J. 1986 Sep;50(3):417-22.

A model for length-regulation in thick filaments of vertebrate skeletal myosin.

Abstract

A mechanism for length regulation in the parallel-packed section of the thick filament is proposed. It is based on experiments done on synthetic, mini- and native filaments, and its primary purpose is to explain the physical basis of the kinetic mechanism for the assembly of synthetic thick filaments from myosin alone. Kinetically, length is regulated by a dissociation rate constant that increases exponentially as the filament grows bi-directionally from its center. Growth ceases at the point of equilibrium between invariant on and length-dependent off rates. The three subfilaments structure of the parallel-packed region of the thick filament is fundamental to the proposed scheme. The intra-subfilament bonding is strong and predominantly ionic in character, whereas the inter-subfilament bonding is relatively weak. These strong and weak interactions participate directly in the strictly sequential mechanism of assembly of dimer subunit observed in the kinetics. A third domain, independent of the sequential mechanism, consists of opposing negative charges on the subfilament surface, juxtaposed at or close to the thick filament axis. The weak and repulsive domains are additively coupled to each other through the rigidity in the subfilaments. Length regulation occurs through the repulsive component rising in intensity more rapidly with length than the initially stronger positive interactions. Growth ceases at the point where the repulsive interactions weaken the attractive interactions to the extent that equilibrium is established between head-to-tail dimer subunit and its binding sites at the tips of the arms of thick filament. This myosin-mediated mechanism, which gives rise to a narrow length distribution, is considered to be fine-tuned by co-polymerizing proteins to give the precise length of the native filament.

PMID:
3756294
PMCID:
PMC1329716
DOI:
10.1016/S0006-3495(86)83477-4
[Indexed for MEDLINE]
Free PMC Article

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