The assembly of immunoglobulin-like modules in titin: implications for muscle elasticity

Improta, Sabina; Krueger, Joanna K.; Gautel, Mathias; Atkinson, R. Andrew; Lefèvre, Jean‐François; Moulton, S; Trewhella, Jill; Pastore, Annalisa

doi:10.1006/jmbi.1998.2028

Cited by 78 publications

(66 citation statements)

References 67 publications

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“…1A measures L c ϭ 72.5 nm. While the extension of this region is predominantly from the PEVK domain, part of this extension represents a contribution from the three folded I27 modules, ϳ4.5 nm/folded I27 domain (22,24), and has to be subtracted from the measured L c . A corrected L c value of 59 nm is consistent with the extension of two PEVK domains (two exon 120 domains, see above; L c ϭ 61.6 nm).…”

Section: Resultsmentioning

confidence: 99%

The Elasticity of Individual Titin PEVK Exons Measured by Single Molecule Atomic Force Microscopy

Sarkar

Caamano

Fernández

2005

Journal of Biological Chemistry

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The I-band region of the giant muscle protein titin contains a large domain enriched for the amino acids proline, glutamate, valine, and lysine and is denoted the PEVK domain. The PEVK domain of titin encodes a random coil shown to be an important factor in the passive elasticity of titin. Muscle-specific splicing of 116 PEVK exons encodes this domain. It has been proposed that proline contents determine the elasticity of the PEVK polypeptide, where the individual exons code for "flexibility cassettes." To test this hypothesis, we have measured the elasticity of three distinct polypeptides encoded by individual PEVK exons (161, 120 and 184) that varied greatly in their proline contents (7, 14, and 37% respectively) and total PEVK contents (55, 70, and 87%). We used single molecule atomic force microscopy techniques to measure the persistence length, p, of the engineered PEVK proteins. Surprisingly, all three exons 161, 120, and 184 coded for proteins with similar values of persistence length, p ‫؍‬ 0.92 ؎ 0.38, 0.89 ؎ 0.42, and 0.98 ؎ 0.4 nm, respectively. We conclude that the PEVK exons encode polypeptides of similar elastic properties, unrelated to their total PEVK contents. Hence, alternative splicing solely adjusts the length of the PEVK domain of titin.

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Section: Resultsmentioning

confidence: 99%

The Elasticity of Individual Titin PEVK Exons Measured by Single Molecule Atomic Force Microscopy

Sarkar

Caamano

Fernández

2005

Journal of Biological Chemistry

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“…76 Both ab initio and rigid body modeling of the SAXS data revealed that the removal of the C0 domain did not perturb the conformation of C1-m-C2 (C1C2), indicating that the overall modular architecture of the protein and spatial organization of the domains are similar to the Ig-repeat scaffold observed in the giant muscle protein titin in which the linkers confer a degree of elasticity to the structure, while maintaining the approximate dispositions of the domains with respect to each other. 77 Mapping the positions of disease mutations associated with familial hypertrophic cardiomyopathy (HCM) onto the SAXS-derived structural model of C0C2 (see Figure 5) indicates that the sites of HCM-causing mutations predominantly cluster along one side of the molecule at the domain interfaces between C1-and m-, and in regions of C1 and C2 identified as binding to myosin DS2 and close to m-domain phosphorylation sites. This modeling led to the proposal that the myosin S2 binding interface spans a region encompassing …”

Section: Cardiac Myosin Binding Protein Cmentioning

confidence: 99%

Invited review: Probing the structures of muscle regulatory proteins using small‐angle solution scattering

Jeffries

Trewhella

2011

Biopolymers

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Small‐angle X‐ray and neutron scattering with contrast variation have made important contributions in advancing our understanding of muscle regulatory protein structures in the context of the dynamic molecular processes governing muscle action. The contributions of the scattering investigations have depended upon the results of key crystallographic, NMR, and electron microscopy experiments that have provided detailed structural information that has aided in the interpretation of the scattering data. This review will cover the advances made using small‐angle scattering techniques, in combination with the results from these complementary techniques, in probing the structures of troponin and myosin binding protein C. A focus of the troponin work has been to understand the isoform differences between the skeletal and cardiac isoforms of this major calcium receptor in muscle. In the case of myosin binding protein C, significant data are accumulating, indicating that this protein may act to modulate the primary calcium signals from troponin, and interest in its biological role has grown because of linkages between gene mutations in the cardiac isoform and serious heart disease. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 505–516, 2011.

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“…It is highly modular: ϳ90% of its mass is composed of repeating Ig-C2 and fibronectin-3-like domains that provide binding sites for myofibrillar proteins (31,32). The remaining ϳ10% consists of unique non-repetitive sequence motifs, including phosphorylation sites, binding sites for muscle-specific calpain proteases, and C-terminal Ser/Thr kinase domains (30,(33)(34)(35).…”

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confidence: 99%

The Hydrophilic Domain of Small Ankyrin-1 Interacts with the Two N-terminal Immunoglobulin Domains of Titin

Kontrogianni‐Konstantopoulos

Bloch

2003

Journal of Biological Chemistry

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Little is known about the mechanisms that organize the internal membrane systems in eukaryotic cells. We are addressing this question in striated muscle, which contains two novel systems of internal membranes, the transverse tubules and the sarcoplasmic reticulum (SR). Small ankyrin-1 (sAnk1) is an ϳ17-kDa transmembrane protein of the SR that concentrates around the Z-disks and M-lines of each sarcomere. We used the yeast twohybrid assay to determine whether sAnk1 interacts with titin, a giant myofibrillar protein that organizes the sarcomere. We found that the hydrophilic cytoplasmic domain of sAnk1 interacted with the two most N-terminal Ig domains of titin, ZIg1 and ZIg2, which are present at the Z-line in situ. Both ZIg1 and ZIg2 were required for binding activity. sAnk1 did not interact with other sequences of titin that span the Z-disk or with Ig domains of titin near the M-line. Titin ZIg1/2 also bound T-cap/ telethonin, a 19-kDa protein of the Z-line. We show that titin ZIg1/2 could form a three-way complex with sAnk1 and T-cap. Our results indicate that titin ZIg1/2 can bind sAnk1 in muscle homogenates and suggest a role for these proteins in organizing the SR around the contractile apparatus at the Z-line.

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The assembly of immunoglobulin-like modules in titin: implications for muscle elasticity

Cited by 78 publications

References 67 publications

The Elasticity of Individual Titin PEVK Exons Measured by Single Molecule Atomic Force Microscopy

The Elasticity of Individual Titin PEVK Exons Measured by Single Molecule Atomic Force Microscopy

Invited review: Probing the structures of muscle regulatory proteins using small‐angle solution scattering

The Hydrophilic Domain of Small Ankyrin-1 Interacts with the Two N-terminal Immunoglobulin Domains of Titin

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