Evidence map›Paper›PMID 24607906›Full record

ArticleBiochemical and biophysical research communications2014

Structure and flexibility of the tropomyosin overlap junction.

Xiaochuan Edward Li, Marek Orzechowski, William Lehman, Stefan Fischer

Abstract read
In one paragraph

Article in Biochemical and biophysical research communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed.

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  19. Atomic resolution probe for allostery in the regulatory thin filament.Proceedings of the National Academy of Sciences of the United States of America · 2016
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Xiaochuan Edward LiDepartment of Physiology and Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA; Computational Biochemistry Group, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, Heidelberg D69120, Germany.
Marek OrzechowskiDepartment of Physiology and Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA; Computational Biochemistry Group, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, Heidelberg D69120, Germany.
William LehmanDepartment of Physiology and Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA. Electronic address: wlehman@bu.edu.
Stefan FischerComputational Biochemistry Group, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, Heidelberg D69120, Germany. Electronic address: stefan.fischer@iwr.uni-heidelberg.de.

Funding

Thin Filaments and Muscle RegulationR37HL036153 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI LEHMAN, WILLIAM J · 2008 to 2017
$4.1M
NHLBI NIH HHS R37 HL036153NHLBI NIH HHS R37HL036153
6 · The paper itself

Abstract

To be effective as a gatekeeper regulating the access of binding proteins to the actin filament, adjacent tropomyosin molecules associate head-to-tail to form a continuous super-helical cable running along the filament surface. Chimeric head-to-tail structures have been solved by NMR and X-ray crystallography for N- and C-terminal segments of smooth and striated muscle tropomyosin spliced onto non-native coiled-coil forming peptides. The resulting 4-helix complexes have a tight coiled-coil N-terminus inserted into a separated pair of C-terminal helices, with some helical unfolding of the terminal chains in the striated muscle peptides. These overlap complexes are distinctly curved, much more so than elsewhere along the superhelical tropomyosin cable. To verify whether the non-native protein adducts (needed to stabilize the coiled-coil chimeras) perturb the overlap, we carried out Molecular Dynamics simulations of head-to-tail structures having only native tropomyosin sequences. We observe that the splayed chains all refold and become helical. Significantly, the curvature of both the smooth and the striated muscle overlap domain is reduced and becomes comparable to that of the rest of the tropomyosin cable. Moreover, the measured flexibility across the junction is small. This and the reduced curvature ensure that the super-helical cable matches the contours of F-actin without manifesting localized kinking and excessive flexibility, thus enabling the high degree of cooperativity in the regulation of myosin accessibility to actin filaments.

Indexed as

ActinsAnimalsCrystallography, X-RayHumansModels, MolecularMolecular Dynamics SimulationMuscle, SkeletalMuscle, SmoothNuclear Magnetic Resonance, BiomolecularProtein Structure, SecondaryProtein Structure, TertiaryRecombinant Fusion ProteinsTropomyosinActinsRecombinant Fusion ProteinsTropomyosinActinCoiled-coilMolecular DynamicsMuscle regulationThin filaments

Identifiers

PMID24607906
PMCPMC4003899

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.