The structural principles of multidomain organization of the giant polypeptide chain of the muscle titin protein: SAXS/WAXS studies during the stretching of oriented titin fibres

Vazina, A.A.; Lanina, N. F.; Alexeev, Dmitry; Bras, Wim; Dolbnya, Igor P.

doi:10.1016/j.jsb.2006.03.025

Cited by 8 publications

(5 citation statements)

References 63 publications

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“…High-resolution structures of titin and obscurin Ig and FnIII domains show that both crystallography and NMR methods result in reliably accurate structures (see Table 1). Complementing these methods, SAXS experimentation is used to generate most low-resolution structures in the literature, although cryo-EM is also sometimes employed [for instance: (Von Castelmur et al, 2008; Jeffries et al, 2011; Al-Khayat et al, 2013) for cryo-EM and (Marino et al, 2005; Vazina et al, 2006; Von Castelmur et al, 2008; Bucher et al, 2010; Tskhovrebova et al, 2010) for SAXS]. For X-ray crystallography, titin, and obscurin domains most frequently crystallize in various concentrations of ammonium sulfate.…”

Section: Ig and Fniii Domainsmentioning

confidence: 99%

Structure of giant muscle proteins

Meyer

Wright

2013

Front. Physiol.

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Giant muscle proteins (e.g., titin, nebulin, and obscurin) play a seminal role in muscle elasticity, stretch response, and sarcomeric organization. Each giant protein consists of multiple tandem structural domains, usually arranged in a modular fashion spanning 500 kDa to 4 MDa. Although many of the domains are similar in structure, subtle differences create a unique function of each domain. Recent high and low resolution structural and dynamic studies now suggest more nuanced overall protein structures than previously realized. These findings show that atomic structure, interactions between tandem domains, and intrasarcomeric environment all influence the shape, motion, and therefore function of giant proteins. In this article we will review the current understanding of titin, obscurin, and nebulin structure, from the atomic level through the molecular level.

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Section: Ig and Fniii Domainsmentioning

confidence: 99%

Structure of giant muscle proteins

Meyer

Wright

2013

Front. Physiol.

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“…Both experimental and computational studies have examined previously the energetic requirements to stretch and unfold titin Ig-domains, both for single domains and for tandem chains (7,26,29,30,35,36,40,43,(82)(83)(84)(85)(86)(87), but most investigations focused on stretching involving strong forces that actually unraveled the secondary structure of individual domains.…”

Section: Tertiary Structure Elasticity Of Z1z2mentioning

confidence: 99%

Secondary and Tertiary Structure Elasticity of Titin Z1Z2 and a Titin Chain Model

Lee

Hsin

Mayans

et al. 2007

Biophysical Journal

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The giant protein titin, which is responsible for passive elasticity in muscle fibers, is built from approximately 300 regular immunoglobulin-like (Ig) domains and FN-III repeats. While the soft elasticity derived from its entropic regions, as well as the stiff mechanical resistance derived from the unfolding of the secondary structure elements of Ig- and FN-III domains have been studied extensively, less is known about the mechanical elasticity stemming from the orientation of neighboring domains relative to each other. Here we address the dynamics and energetics of interdomain arrangement of two adjacent Ig-domains of titin, Z1, and Z2, using molecular dynamics (MD) simulations. The simulations reveal conformational flexibility, due to the domain-domain geometry, that lends an intermediate force elasticity to titin. We employ adaptive biasing force MD simulations to calculate the energy required to bend the Z1Z2 tandem open to identify energetically feasible interdomain arrangements of the Z1 and Z2 domains. The finding is cast into a stochastic model for Z1Z2 interdomain elasticity that is generalized to a multiple domain chain replicating many Z1Z2-like units and representing a long titin segment. The elastic properties of this chain suggest that titin derives so-called tertiary structure elasticity from bending and twisting of its domains. Finally, we employ steered molecular dynamics simulations to stretch individual Z1 and Z2 domains and characterize the so-called secondary structure elasticity of the two domains. Our study suggests that titin's overall elastic response at weak force stems from a soft entropic spring behavior (not described here), from tertiary structure elasticity with an elastic spring constant of approximately 0.001-1 pN/A and, at strong forces, from secondary structure elasticity.

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“…Fibre diffraction during stretching suggests that they consist of an aperiodic array of rigid domains linked by flexible short loops. 30 The great challenge is now to unravel the details of the mechanism of conversion of chemical to mechanical energy, which must cover several orders of magnitude in time. Indeed, the actual release of energy must occur in a very short time in systems like muscle, 31 whereas the time scale of structural changes is essentially associated with constrained diffusion processes rather than with those characteristic of the breaking or making of chemical bonds (attoseconds to femtoseconds).…”

Section: Biological Applicationsmentioning

confidence: 99%

“…The giant muscle protein titin is a multidomain fibrous protein consisting of an array of Ig and FnIII domains connected by short flexible loops. 30 In this case one can only usefully study the solution structure of fragments like titin/telethonin complexes, for which a tentative model including parts missing in the crystal structure was obtained. 128 Combined NMR and SAXS studies also indicate significant differences between the crystal and solution structures of the Ig doublet Z1Z2 fragment of titin.…”

Section: Biological Applicationsmentioning

confidence: 99%