Evidence map›Paper›PMID 25726728›Full record

ArticleArchives of biochemistry and biophysics2015

Phosphorylation of Ser283 enhances the stiffness of the tropomyosin head-to-tail overlap domain.

William Lehman, Greg Medlock, Xiaochuan Edward Li, Worawit Suphamungmee, An-Yue Tu, Anja Schmidtmann, Zoltán Ujfalusi, Stefan Fischer, Jeffrey R Moore, Michael A Geeves and 1 more

Open access · greenAbstract read
In one paragraph

Article in Archives of biochemistry and biophysics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
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

19 citing papers in PubMed, 34 citations in OpenAlex.

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  18. Structural determinants of muscle thin filament cooperativity.Archives of biochemistry and biophysics · 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

11 authors at 4 institutions in 3 countries.

William LehmanDepartment of Physiology & Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA. Electronic address: wlehman@bu.edu.
Greg MedlockDepartment of Bioengineering, University of Washington, South Research Building, 950 Republican Street, Seattle, WA 98109, USA.
Xiaochuan Edward LiDepartment of Physiology & Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
Worawit SuphamungmeeDepartment of Physiology & Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
An-Yue TuDepartment of Bioengineering, University of Washington, South Research Building, 950 Republican Street, Seattle, WA 98109, USA.
Anja SchmidtmannSchool of Biosciences, Stacey Building, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Zoltán UjfalusiSchool of Biosciences, Stacey Building, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Stefan FischerComputational Biochemistry Group, Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Im Neuenheimer Feld 368, Heidelberg D69120, Germany.
Jeffrey R MooreDepartment of Physiology & Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA.
Michael A GeevesSchool of Biosciences, Stacey Building, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Michael RegnierDepartment of Bioengineering, University of Washington, South Research Building, 950 Republican Street, Seattle, WA 98109, USA.
Boston University · USUniversity of Kent · GBUniversity of Washington · USHeidelberg University · DE

Funding

Genetic and Molecular Basis of Congenital ContracturesR01HD048895 · NICHD · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH · 2005 to 2016
$4.3M
Thin Filaments and Muscle RegulationR37HL036153 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI LEHMAN, WILLIAM J · 2008 to 2017
$4.1M
Molecular Mechanics of Mutant Cardiac MyosinR01HL077280 · NHLBI · UNIVERSITY OF MASSACHUSETTS LOWELL · PI MOORE, JEFFREY R · 2005 to 2014
$3.3M
Cooperativity in the Cardiac Myofilament Interactome in Health and DiseaseR01HL123774 · NHLBI · UNIVERSITY OF MASSACHUSETTS LOWELL · PI MOORE, JEFFREY R · 2016 to 2019
$1.6M
British Heart Foundation 30200British Heart Foundation PG/13/75/30200NHLBI NIH HHS R01HL011197NHLBI NIH HHS R01 HL077280NHLBI NIH HHS R01HL077280NHLBI NIH HHS R01 HL123774NHLBI NIH HHS R37 HL036153NHLBI NIH HHS R37HL036153NICHD NIH HHS R01 HD048895NICHD NIH HHS R01HD048895Wellcome Trust 085309
6 · The paper itself

Abstract

The ends of coiled-coil tropomyosin molecules are joined together by nine to ten residue-long head-to-tail "overlapping domains". These short four-chained interconnections ensure formation of continuous tropomyosin cables that wrap around actin filaments. Molecular Dynamics simulations indicate that the curvature and bending flexibility at the overlap is 10-20% greater than over the rest of the molecule, which might affect head-to-tail filament assembly on F-actin. Since the penultimate residue of striated muscle tropomyosin, Ser283, is a natural target of phosphorylating enzymes, we have assessed here if phosphorylation adjusts the mechanical properties of the tropomyosin overlap domain. MD simulations show that phosphorylation straightens the overlap to match the curvature of the remainder of tropomyosin while stiffening it to equal or exceed the rigidity of canonical coiled-coil regions. Corresponding EM data on phosphomimetic tropomyosin S283D corroborate these findings. The phosphorylation-induced change in mechanical properties of tropomyosin likely results from electrostatic interactions between C-terminal phosphoSer283 and N-terminal Lys12 in the four-chain overlap bundle, while promoting stronger interactions among surrounding residues and thus facilitating tropomyosin cable assembly. The stiffening effect of D283-tropomyosin noted correlates with previously observed enhanced actin-tropomyosin activation of myosin S1-ATPase, suggesting a role for the tropomyosin phosphorylation in potentiating muscle contraction.

Indexed as

AnimalsMiceMolecular Dynamics SimulationMutationPhosphorylationProtein Structure, TertiarySerineTropomyosinSerineTropomyosinActinCardiomyopathyMolecular DynamicsMuscle regulationPhosphorylationTropomyosin

Identifiers

PMID25726728
PMCPMC4385494
OpenAlexW2130810379

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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.