Polymorphism in tropomyosin structure and function

  • Miro Janco
  • Worawit Suphamungmee
  • Xiaochuan Li
  • William Lehman
  • Sherwin S. Lehrer
  • Michael A. Geeves
Review

Abstract

Tropomyosins (Tm) in humans are expressed from four distinct genes and by alternate splicing >40 different Tm polypeptide chains can be made. The functional Tm unit is a dimer of two parallel polypeptide chains and these can be assembled from identical (homodimer) or different (heterodimer) polypeptide chains provided both chains are of the same length. Since most cells express multiple isoforms of Tm, the number of different homo and heterodimers that can be assembled becomes very large. We review the mechanism of dimer assembly and how preferential assembly of some heterodimers is driven by thermodynamic stability. We examine how in vitro studies can reveal functional differences between Tm homo and heterodimers (stability, actin affinity, flexibility) and the implication for how there could be selection of Tm isomers in the assembly on to an actin filament. The role of Tm heterodimers becomes more complex when mutations in Tm are considered, such as those associated with cardiomyopathies, since mutations can appear in only one of the chains.

Keywords

Heterodimers and homodimers Tropomyosin isoforms Coiled-coils Actin Cardiomyopathy mutations 

Abbreviations

Tm

Tropomyosin

Tn

Troponin

HCM

Hypertrophic cardiomyopathy

DCM

Dilated cardiomyopathy

αα*

Heterodimer of αTm where one chain carries the mutation

HMW

High molecular weight

LMW

Low molecular weight

GG

Chicken gizzard αTm

RR

Rabbit skeletal αTm

PLa

Apparent persistence length

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Miro Janco
    • 1
  • Worawit Suphamungmee
    • 2
  • Xiaochuan Li
    • 2
  • William Lehman
    • 2
  • Sherwin S. Lehrer
    • 3
  • Michael A. Geeves
    • 1
  1. 1.School of BiosciencesUniversity of KentCanterburyUK
  2. 2.Department of Physiology and BiophysicsBoston University School of MedicineBostonUSA
  3. 3.Boston Biomedical Research InstituteWatertownUSA

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