The evolution of titin and related giant muscle proteins

  title={The evolution of titin and related giant muscle proteins},
  author={Desmond G. Higgins and Siegfried Labeit and Mathias Gautel and Toby J. Gibson},
  journal={Journal of Molecular Evolution},
Titin and twitchin are giant proteins expressed in muscle. They are mainly composed of domains belonging to the fibronectin class III and immunoglobulin c2 families, repeated many times. In addition, both proteins have a protein kinase domain near the C-terminus. This paper explores the evolution of these and related muscle proteins in an attempt to determine the order of events that gave rise to the different repeat patterns and the order of appearance of the proteins. Despite their great… 
Properties of Titin Immunoglobulin and Fibronectin-3 Domains*
The Ig and Fn3 domains are important in titin interactions, whereas the levels of interdomain mobility and structural stability relate directly to mechanical functions.
Mechanochemical evolution of the giant muscle protein titin as inferred from resurrected proteins
It is hypothesized that mechanical adjustments in titin contributed to physiological changes that allowed the muscular development and diversity of modern tetrapods and is estimated to correlate with animal body size, allowing us to estimate the sizes of extinct species.
Huxleys' Missing Filament: Form and Function of Titin in Vertebrate Striated Muscle.
Although superthin filaments were inferred from early experiments on muscle, decades passed before their existence was accepted, recent studies demonstrate unequivocally that titin stiffness increases upon muscle activation, but the mechanisms are only now being uncovered.
Invertebrate muscles: muscle specific genes and proteins.
This is the first of a projected series of canonic reviews covering all invertebrate muscle literature prior to 2005 and covers muscle genes and proteins except those involved in excitation-contraction coupling and those forming ligand- and voltage-dependent channels.
A Titan but not Necessarily a Ruler: Assessing the Role of Titin During Thick Filament Patterning and Assembly
An overview of the many different roles of titin in the development and function of striated muscle is given, and the validity of the “molecular ruler” model of myofibrillogenesis in light of the current literature is addressed.
Conformational plasticity and evolutionary analysis of the myotilin tandem Ig domains
It is hypothesised that the conformational plasticity of the Ig domain pair in its unbound form is part of the binding partner recognition mechanism of the inter-domain hinge mechanism.
Species variations in cDNA sequence and exon splicing patterns in the extensible I-band region of cardiac titin: relation to passive tension
Shorter N2B unique and N2BA PEVK segments may also contribute to the greater passive tension in cardiac muscle from rats as well as human and dog cardiac muscle.
Structural insights into the basis and evolution of interactions in multi-subunit protein assemblies. tryptophan synthase and titin FNIII-repeats
This study aims at gaining an insight into the evolutionary shaping of proteins surfaces for hetero-complex formation by studying two systems at an early stage of development: Tryptophan Synthase B2b (TrpB2b) from S. solfataricus and the modular interfaces of the poly-FNIII tandems in the muscle filament titin.
The sarcomeric cytoskeleton: from molecules to motion
The sarcomeric cytoskeleton is a system of proteins specific to striated muscle that play a key role in organising the contractile machinery, and integrating and regulating its mechanics and signalling functions.


Towards a molecular understanding of titin.
It is concluded that A‐band titin is likely to be involved in the ordered assembly of the vertebrate thick filament.
Drosophila has a twitchin/titin-related gene that appears to encode projectin.
It is reported here that Drosophila has a single-copy gene containing the two-motif amino acid sequence pattern that characterizes twitchin and titin, a muscle protein thought to play a structural role in asynchronous flight muscle but may have a role like that of twitchin in synchronous muscle.
A regular pattern of two types of 100-residue motif in the sequence of titin
It is shown that partial titin complementary DNAs encode a regular pattern of two types of 100-residue motif, each of which probably folds into a separate domain type.
Regulatory and structural motifs of chicken gizzard myosin light chain kinase.
Results indicate that the amino acid sequence of smMLCK encodes multiple functional motifs in addition to the catalytic domain, which is defined as being contained within and probably identical to the pseudosubstrate domain.
A comparative study of high molecular weight proteins in various types of muscle across the animal kingdom.
A wide range of phyla have been surveyed by SDS-PAGE for the new large proteins of the myofibril, and Connectin (or titin) appears to be widely distributed and nebulin shares the same distribution in vertebrate muscles except for its notable absence in all heart muscle examined.
Isolation and characterization of a cDNA clone encoding avian skeletal muscle C-protein: an intracellular member of the immunoglobulin superfamily.
  • S. Einheber, D. Fischman
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1990
C-protein is a thick filament-associated protein located in the crossbridge region of vertebrate striated muscle A bands. Its function is unknown. To improve our understanding of its primary
Sequence of an unusually large protein implicated in regulation of myosin activity in C. elegans
Homologies of the sequence of twit-chin have unexpected similarities to the sequences of proteins of the immunoglobulin superfamily, cell adhesion molecules and vertebrate muscle proteins, including myosin light-chain kinase, which indicate that the protein is involved in a novel mechanism of myOSin regulation.
Drosophila projectin: relatedness to titin and twitchin and correlation with lethal (4) 102 CDa and bent-Dominant mutants
It is proposed that this hatching failure in Drosophila melanogaster is due to muscle weakness caused by projectin defects, and two mutants mapped to the location of the projectin gene in the 102C subdivision of chromosome 4, lethal(4)102 CDa and bent-Dominant, have DNA rearrangements within their projectin genes.
Myogenesis in the mouse embryo: differential onset of expression of myogenic proteins and the involvement of titin in myofibril assembly
The results indicate that the putative elastic titin filaments act as integrators during skeletal muscle development in mouse embryogenesis and that the known interaction of the I-Z-I brushes with the A bands occurs at a later developmental stage.