Different pressure–temperature behavior of the structured and unstructured regions of titin

Somkuti, Judit; Mártonfalvi, Zsolt; Kellermayer, Miklós; Smeller, László

doi:10.1016/j.bbapap.2012.10.001

Cited by 24 publications

(28 citation statements)

References 56 publications

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“…We found that I91 does not react with GSSG at 37°C, implying that the cysteines in native I91 are inaccessible to GSSG under physiological conditions (Figure 1D). However, I91 became S-glutathionylated at temperatures higher than 55°C, which have been shown to unfold I91 (Somkuti et al, 2013) (Figure 1D). S-glutathionylation could be reversed by incubation with 50 mM dithiothreitol (DTT), a strong reducing agent that cleaves the mixed disulfide between cysteine and glutathione (Figure 1D).…”

Section: Resultsmentioning

confidence: 97%

S-Glutathionylation of Cryptic Cysteines Enhances Titin Elasticity by Blocking Protein Folding

Alegre-Cebollada

Kosuri

Giganti

et al. 2014

Cell

181

232

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The giant elastic protein titin is a determinant factor in how much blood fills the left ventricle during diastole, and thus in the etiology of heart disease. Titin has been identified as a target of S-glutathionylation, an end product of the nitric oxide signaling cascade that increases cardiac muscle elasticity. However, it is unknown how S-glutathionylation may regulate the elasticity of titin and cardiac tissue. Here we show that mechanical unfolding of titin immunoglobulin (Ig) domains exposes buried cysteine residues, which then can be S-glutathionylated. S-glutathionylation of cryptic cysteines greatly decreases the mechanical stability of the parent Ig domain as well as its ability to fold. Both effects favor a more extensible state of titin. Furthermore we demonstrate that S-glutathionylation of cryptic cysteines in titin mediates mechano-chemical modulation of the elasticity of human cardiomyocytes. We propose that posttranslational modification of cryptic residues is a general mechanism to regulate tissue elasticity.

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Section: Resultsmentioning

confidence: 97%

S-Glutathionylation of Cryptic Cysteines Enhances Titin Elasticity by Blocking Protein Folding

Alegre-Cebollada

Kosuri

Giganti

et al. 2014

Cell

181

232

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“…The PEVK domain of titin was investigated by FTIR spectroscopy under various pH and temperature conditions (Somkuti et al 2013b). Since these experiments did not reveal any region where the polypeptide chain would adopt any ordered structure, the second situation discussed above is more probable for PEVK, which means that this protein domain has always negative G.…”

Section: Intrinsically Disordered Proteins (Idps)mentioning

confidence: 99%

“…The pressure-temperature phase diagram of I27 was determined using FTIR and tryptophan fluorescence spectroscopies in our laboratory (Fig. 2.9) (Somkuti et al 2013b). The most remarkable feature of the diagram is the appearance of the molten globule state at slightly elevated temperature in the low-pressure region.…”

Section: Ig27 Of Titinmentioning

confidence: 99%

Protein Denaturation on p-T Axes – Thermodynamics and Analysis

Smeller

2015

Subcellular Biochemistry

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Proteins are essential players in the vast majority of molecular level life processes. Since their structure is in most cases substantial for their correct function, study of their structural changes attracted great interest in the past decades. The three dimensional structure of proteins is influenced by several factors including temperature, pH, presence of chaotropic and cosmotropic agents, or presence of denaturants. Although pressure is an equally important thermodynamic parameter as temperature, pressure studies are considerably less frequent in the literature, probably due to the technical difficulties associated to the pressure studies. Although the first steps in the high-pressure protein study have been done 100 years ago with Bridgman's ground breaking work, the field was silent until the modern spectroscopic techniques allowed the characterization of the protein structural changes, while the protein was under pressure. Recently a number of proteins were studied under pressure, and complete pressure-temperature phase diagrams were determined for several of them. This review summarizes the thermodynamic background of the typical elliptic p-T phase diagram, its limitations and the possible reasons for deviations of the experimental diagrams from the theoretical one. Finally we show some examples of experimentally determined pressure-temperature phase diagrams.

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“…Somkuti et al broadened the range of experimental conditions traditionally used for structural and conformational analysis of proteins by considering the effects of a wide range of pressure and temperature on the ordered and disordered domains of titin 89 . This was done using Fourier transform infrared (FTIR) and fluorescence spectroscopy combined with a diamond anvil cell that allowed investigation of protein secondary structure and fluorescent parameters across the broad range of pressure (0–16 kbar), temperature (0–100°C), pD (3–10.5), and different solvent conditions 89 .…”

Section: Methods For the Idp/idpr Analysismentioning

confidence: 99%

“…This was done using Fourier transform infrared (FTIR) and fluorescence spectroscopy combined with a diamond anvil cell that allowed investigation of protein secondary structure and fluorescent parameters across the broad range of pressure (0–16 kbar), temperature (0–100°C), pD (3–10.5), and different solvent conditions 89 . As targets proteins, they used an ordered Ig domain (I27) and a 171-residue-long fragment (polyE) of the disordered PEVK domain derived from titin, 89 a giant elastic protein (canonical form of human titin consists of 34,350 residues) responsible for striated-muscle elasticity, which is known to possess a lot of disorder 90 . This analysis revealed that the PolyE domain preserved its disordered characteristics in the whole range of conditions studied, whereas structured I27 possessed an intricate conformational response to changing conditions that can only be described by the complex temperature-pressure phase diagram 89 …”

Section: Methods For the Idp/idpr Analysismentioning

confidence: 99%

Digested disorder

Uversky

2013

Intrinsically Disordered Proteins

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The current literature on intrinsically disordered proteins is blooming. A simple PubMed search for “intrinsically disordered protein OR natively unfolded protein” returns about 1,800 hits (as of June 17, 2013), with many papers published quite recently. To keep interested readers up to speed with this literature, we are starting a “Digested Disorder” project, which will encompass a series of reader’s digest type of publications aiming at the objective representation of the research papers and reviews on intrinsically disordered proteins. The only two criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest covers papers published during the period of January, February and March of 2013. The papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

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Different pressure–temperature behavior of the structured and unstructured regions of titin

Cited by 24 publications

References 56 publications

S-Glutathionylation of Cryptic Cysteines Enhances Titin Elasticity by Blocking Protein Folding

S-Glutathionylation of Cryptic Cysteines Enhances Titin Elasticity by Blocking Protein Folding

Protein Denaturation on p-T Axes – Thermodynamics and Analysis

Digested disorder

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