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          Institute: MPI für medizinische Forschung     Collection: Muskelforschung     Display Documents

ID: 565798.0, MPI für medizinische Forschung / Muskelforschung
The Shape and Flexibility of Tropomyosin Coiled Coils:
Implications for Actin Filament Assembly
and Regulation
Translation of Title:The Shape and Flexibility of Tropomyosin Coiled Coils:
Implications for Actin Filament Assembly
and Regulation
Authors:Li, Xiaochuan Edward; Holmes, Kenneth C.; Lehman, William; Jung, Hyun Suk; Fischer, Stefan
Date of Publication (YYYY-MM-DD):2010-01-15
Title of Journal:Journal of Molecular Biology
Journal Abbrev.:Journal of Molecular Biology
Issue / Number:2
Start Page:327
End Page:339
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Wrapped superhelically around actin filaments, the coiled−coil α−helices of
tropomyosin regulate muscle contraction by cooperatively blocking or
exposing myosin−binding sites on actin. In non−muscle cells, tropomyosin
additionally controls access of actin−binding proteins involved in cytoskeletal
actin filament maintenance and remodeling. Tropomyosin's global
shape and flexibility play a key role in the assembly, maintenance, and
regulatory switching of thin filaments yet remain insufficiently characterized.
Here, electron microscopy and molecular dynamics simulations
yielded conformations of tropomyosin closely resembling each other. The
electron microscopy and simulations show that isolated tropomyosin has an
average curved conformation with a design well matched to its superhelical
shape on F−actin. In addition, they show that tropomyosin bends smoothly
yet anisotropically about its distinctive helically curved conformation,
without any signs of unfolding, chain separation, localized kinks, or joints.
Previous measurements, assuming tropomyosin to be straight on average,
mistakenly suggested considerable flexibility (with persistence lengths only
∼3 times the protein's length). However, taking the curved average
structure determined here as reference for the flexibility measurements
yields a persistence length of ∼12 lengths, revealing that tropomyosin
actually is semirigid. Corresponding simulation of a triple mutant (A74L−
A78V−A81L) with weak actin affinity shows that it lacks shape complementarity
to F−actin. Thus, tropomyosin's pre−shaped semirigid architecture
is essential for the assembly of actin filaments. Further, we propose that
once bound to thin filaments, tropomyosin will be stiff enough to act as a
cooperative unit and move on actin in a concerted way between known
regulatory states
Free Keywords:actin; tropomyosin; coiled coils; electron microscopy; molecular
Last Change of the Resource (YYYY-MM-DD):--
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Biophysik/Protein - Kristallographie XDS
MPI für medizinische Forschung/Abteilung Biophysik/Muskelforschung
MPI für medizinische Forschung/Abteilung Biophysik
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