Thermal transitions in the structure of tubulin

Mozo-Villarías, Angel; Morros, Antoni; Andreu, José Manuel

doi:10.1007/bf00183318

Cited by 18 publications

(14 citation statements)

References 25 publications

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“…Theoretical spectra were calculated by applying a Gaussian function to each exciton transition using an assumed full-width half maximum value of 3,500 cm -1 , which is commonly observed for Trp [144][145]. These were then compared to experimental absorption, CD, and LD spectra adapted from Mozzo-Villarías et al [146], Clark et al [147], and Marrington et al [148], respectively.…”

Section: Alignment With Experimental Spectramentioning

confidence: 99%

Oxidative species-induced excitonic transport in tubulin aromatic networks: Potential implications for neurodegenerative disease

Kurian

Obisesan

Craddock

2017

Journal of Photochemistry and Photobiology B: Biology

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Oxidative stress is a pathological hallmark of neurodegenerative tauopathic disorders such as Alzheimer’s disease and Parkinson’s disease-related dementia, which are characterized by altered forms of the microtubule-associated protein (MAP) tau. MAP tau is a key protein in stabilizing the microtubule architecture that regulates neuron morphology and synaptic strength. When MAP tau is degraded in tauopathic disorders, neuron dysfunction results. The precise role of reactive oxygen species (ROS) in the tauopathic disease process, however, is poorly understood. Classically, mitochondrial dysfunction has been viewed as the major source of oxidative stress and has been shown to precede tau and amyloid pathology in various dementias, but the exact mechanisms are not clear. It is known that the production of ROS by mitochondria can result in ultraweak photon emission (UPE) within cells. While of low intensity, surrounding proteins within the cytosol can still absorb these energetic photons via aromatic amino acids (e.g., tryptophan and tyrosine). One likely absorber of these photons is the microtubule cytoskeleton, as it forms a vast network spanning neurons, is highly colocalized with mitochondria, and shows a high density of aromatic amino acids. Functional microtubule networks may traffic this ROS-generated endogenous photon energy for cellular signaling, or they may serve as dissipaters/conduits of such energy to protect the cell from potentially harmful effects. Experimentally, after in vitro exposure to exogenous photons, microtubules have been shown to reorient and reorganize in a dose-dependent manner with the greatest effect being observed around 280 nm, in the tryptophan and tyrosine absorption range. In this paper, recent modeling efforts based on ambient temperature experiment are presented, showing that tubulin polymers can feasibly absorb and channel these photoexcitations via resonance energy transfer, on the order of dendritic length scales and neuronal fine structure. Since microtubule networks are compromised in tauopathic diseases such as Alzheimer’s and Parkinson’s dementias, patients with these illnesses would be unable to support effective channeling of these photons for signaling or dissipation. Consequent emission surplus due to increased UPE production or decreased ability to absorb and transfer may lead to increased cellular oxidative damage, thus hastening the neurodegenerative process.

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Section: Alignment With Experimental Spectramentioning

confidence: 99%

Oxidative species-induced excitonic transport in tubulin aromatic networks: Potential implications for neurodegenerative disease

Kurian

Obisesan

Craddock

2017

Journal of Photochemistry and Photobiology B: Biology

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“…The soluble form of tubulin is highly sensitive to denaturation, but it is protected when incorporated into microtubules (31,32). Thus, we asked whether tubulin aggregation would be reduced in the presence of microtubules.…”

Section: Characterization Of the Thermal Aggregation Of Tubulin-mentioning

confidence: 99%

The 90-kDa Heat Shock Protein Hsp90 Protects Tubulin against Thermal Denaturation

Weis

Moullintraffort

Heichette

et al. 2010

Journal of Biological Chemistry

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Hsp90 and tubulin are among the most abundant proteins in the cytosol of eukaryotic cells. Although Hsp90 plays key roles in maintaining its client proteins in their active state, tubulin is essential for fundamental processes such as cell morphogenesis and division. Several studies have suggested a possible connection between Hsp90 and the microtubule cytoskeleton. Because tubulin is a labile protein in its soluble form, we investigated whether Hsp90 protects it against thermal denaturation. Both proteins were purified from porcine brain, and their interaction was characterized in vitro by using spectrophotometry, sedimentation assays, video-enhanced differential interference contrast light microscopy, and native polyacrylamide gel electrophoresis. Our results show that Hsp90 protects tubulin against thermal denaturation and keeps it in a state compatible with microtubule polymerization. We demonstrate that Hsp90 cannot resolve tubulin aggregates but that it likely binds early unfolding intermediates, preventing their aggregation. Protection was maximal at a stoichiometry of two molecules of Hsp90 for one of tubulin. This protection does not require ATP binding and hydrolysis by Hsp90, but it is counteracted by geldanamycin, a specific inhibitor of Hsp90.Chaperones are essential for cell life because of their involvement in the folding of newly synthesized proteins. Among the chaperones, the heat-shock protein of 90 kDa (Hsp90) 3 is one of the most abundant and ubiquitously expressed cellular proteins (10 -50 M (1)) with a main function of helping other proteins maintain their conformation in an active state. Several client proteins of Hsp90 involved in cell proliferation and apoptosis (such as protein kinases and transcription factors) have been described (2-5). Although Hsp90 is fundamental for the life of normal cells, it also protects mutated proteins against cellular degradation, thus promoting cancer cell survival (6). Therefore, considerable efforts have been made to find inhibitors of its activity (7,8).Over the past decade several studies have suggested a possible relationship between Hsp90 and the microtubule cytoskeleton (9 -15). Tubulin is a highly concentrated cellular protein (10 -20 M (16)) and is the building block of microtubules, which are involved in several crucial processes such as cell division and morphogenesis, compartmentalization, and organelle movement. Its fundamental role in the architecture and functioning of the mitotic spindle has also made this protein a classical target of antimitotic drugs. A direct interaction between Hsp90 and tubulin has previously been described (9), but Hsp90 is also known to interact with other chaperones and co-chaperones to perform its function (17-19). Therefore, whether Hsp90 can protect tubulin against denaturation in the absence of other factors remains unknown.In this study we investigated the direct interaction between tubulin and Hsp90, both purified from porcine brain. Tubulin was subjected to thermal denaturation in the absence and in the pres...

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“…10).The enthalpy change associated with the low temperature shoulder can be roughly estimated to be ϳ30 Ϯ 5 kcal⅐mol Ϫ1 . The CD spectra of thermally denatured tubulin has residual ␤ sheet secondary structure (60). The apparent biphasic denaturation of tubulin at subsaturating levels of Mg 2ϩ could be generated by different processes such as kinetic stabilization of unfolding intermediates, uncoupling of ␣-and ␤-subunit denaturation, or association of the denatured state.…”

Section: Role Of High Affinity Mg 2ϩ In Tubulin Stabilitymentioning

confidence: 99%

Control of the Structural Stability of the Tubulin Dimer by One High Affinity Bound Magnesium Ion at Nucleotide N-site

Menéndez¹,

Rivas²,

Díaz³

et al. 1998

Journal of Biological Chemistry

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Thermal transitions in the structure of tubulin

Cited by 18 publications

References 25 publications

Oxidative species-induced excitonic transport in tubulin aromatic networks: Potential implications for neurodegenerative disease

Oxidative species-induced excitonic transport in tubulin aromatic networks: Potential implications for neurodegenerative disease

The 90-kDa Heat Shock Protein Hsp90 Protects Tubulin against Thermal Denaturation

Control of the Structural Stability of the Tubulin Dimer by One High Affinity Bound Magnesium Ion at Nucleotide N-site

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