Aggregates Sealed by Ions

Penna, Giovanni La; Morante, Silvia

doi:10.1007/978-1-0716-1546-1_14

“…In this configuration, after a first metal ion is bound, the other metal-binding site allegedly present in the acid ridge is “obscured” by the extended N-terminal tail and becomes unattainable by a second metal ion. The Co 2+ “sealing” ability we are invoking here is in agreement with the large body of experimental work that assigns a role to metal ions as structural stabilizers in disordered peptides and protein folding processes (see La Penna and Morante (2021) for a recent review on this issue).…”

Section: Discussionsupporting

confidence: 86%

Metal Ion Binding in Wild-Type and Mutated Frataxin: A Stability Study

Morante

¹

,

Botticelli²,

Chiaraluce³

et al. 2022

Front. Mol. Biosci.

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This work studies the stability of wild-type frataxin and some of its variants found in cancer tissues upon Co2+ binding. Although the physiologically involved metal ion in the frataxin enzymatic activity is Fe2+, as it is customarily done, Co2+ is most often used in experiments because Fe2+ is extremely unstable owing to the fast oxidation reaction Fe2+ → Fe3+. Protein stability is monitored following the conformational changes induced by Co2+ binding as measured by circular dichroism, fluorescence spectroscopy, and melting temperature measurements. The stability ranking among the wild-type frataxin and its variants obtained in this way is confirmed by a detailed comparative analysis of the XAS spectra of the metal-protein complex at the Co K-edge. In particular, a fit to the EXAFS region of the spectrum allows positively identifying the frataxin acidic ridge as the most likely location of the metal-binding sites. Furthermore, we can explain the surprising feature emerging from a detailed analysis of the XANES region of the spectrum, showing that the longer 81-210 frataxin fragment has a smaller propensity for Co2+ binding than the shorter 90-210 one. This fact is explained by the peculiar role of the N-terminal disordered tail in modulating the protein ability to interact with the metal.

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“…An important point to take into account is that the coordination chemistry of Cu II and Cu I are remarkably different. Differences are quite evident when Cu ions are bound to flexible peptides or IDPs [12, 13] . Indeed, flexible peptide chains can more easily adopt the local peptide structures around the metal ion that fit with the coordination preferences of either Cu II or Cu I .…”

Section: Figurementioning

confidence: 99%

“…Dierences are quite evident when Cu ions are bound to exible peptides or IDPs. [12,13] [1416] (see Figure 1). Cu(II) is predominantly coordinated in a distorted square-pyramidal geometry via 3 nitrogen and 1 oxygen equatorial ligands and a weaker O axial ligand.…”

mentioning

confidence: 99%

“…Differences are quite evident when Cu ions are bound to flexible peptides or IDPs. [12,13] Indeed, flexible peptide chains can more easily adopt the local peptide structures around the metal ion that fit with the coordination preferences of either Cu II or Cu I . For instance, in the case of the Aβ peptide, both Cu II and Cu I bind to the N-terminal domain (Aβ 1-16 ) [14][15][16] (see Figure 1).…”

mentioning

confidence: 99%

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Chasing the Elusive “In‐Between” State of the Copper‐Amyloid β Complex by X‐ray Absorption through Partial Thermal Relaxation after Photoreduction

Falcone

¹

,

Nobili

²

,

Okafor

³

et al. 2023

Angewandte Chemie

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The redox activity of Cu ions bound to the amyloid‐β (Aβ) peptide is implicated as a source of oxidative stress in the context of Alzheimer's disease. In order to explain the efficient redox cycling between CuII‐Aβ (distorted square‐pyramidal) and CuI‐Aβ (digonal) resting states, the existence of a low‐populated “in‐between” state, prone to bind Cu in both oxidation states, has been postulated. Here, we exploited the partial X‐ray induced photoreduction at 10 K, followed by a thermal relaxation at 200 K, to trap and characterize by X‐ray Absorption Spectroscopy (XAS) a partially reduced Cu‐Aβ1–16 species different from the resting states. Remarkably, the XAS spectrum is well‐fitted by a previously proposed model of the “in‐between” state, hence providing the first direct spectroscopic characterization of an intermediate state. The present approach could be used to explore and identify the catalytic intermediates of other relevant metal complexes.

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Chasing the Elusive “In‐Between” State of the Copper‐Amyloid β Complex by X‐ray Absorption through Partial Thermal Relaxation after Photoreduction

Falcone

¹

,

Nobili

²

,

Okafor

³

et al. 2023

Self Cite

View full text Add to dashboard Cite

The redox activity of Cu ions bound to the amyloid‐β (Aβ) peptide is implicated as a source of oxidative stress in the context of Alzheimer's disease. In order to explain the efficient redox cycling between CuII‐Aβ (distorted square‐pyramidal) and CuI‐Aβ (digonal) resting states, the existence of a low‐populated “in‐between” state, prone to bind Cu in both oxidation states, has been postulated. Here, we exploited the partial X‐ray induced photoreduction at 10 K, followed by a thermal relaxation at 200 K, to trap and characterize by X‐ray Absorption Spectroscopy (XAS) a partially reduced Cu‐Aβ1–16 species different from the resting states. Remarkably, the XAS spectrum is well‐fitted by a previously proposed model of the “in‐between” state, hence providing the first direct spectroscopic characterization of an intermediate state. The present approach could be used to explore and identify the catalytic intermediates of other relevant metal complexes.

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Aggregates Sealed by Ions

Cited by 3 publications

References 101 publications

Metal Ion Binding in Wild-Type and Mutated Frataxin: A Stability Study

Metal Ion Binding in Wild-Type and Mutated Frataxin: A Stability Study

Chasing the Elusive “In‐Between” State of the Copper‐Amyloid β Complex by X‐ray Absorption through Partial Thermal Relaxation after Photoreduction

Chasing the Elusive “In‐Between” State of the Copper‐Amyloid β Complex by X‐ray Absorption through Partial Thermal Relaxation after Photoreduction

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