Cysteine oxidation to the sulfinic acid induces oxoform-specific lanthanide binding and fluorescence in a designed peptide

Urmey, Andrew R.; Zondlo, Neal J.

doi:10.1016/j.freeradbiomed.2020.02.020

Cited by 6 publications

(11 citation statements)

References 80 publications

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“…The crystal structure of Os PRT6-UBR in complex with a tripeptide, Arg-Asp-Gly, a mimic of the Cys-Arg/N-degron physiological substrate 25,26 , was determined at 1.6 Å resolution (Fig. 2a and Supplementary Table 1).…”

Section: Resultsmentioning

confidence: 99%

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Structural analyses of the plant PRT6-UBR box in the Cys-Arg/N-degron pathway and insights into the plant submergence response

Kim

Lin

et al. 2022

Preprint

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The submergence response in higher plants is highly dependent on the protein stability of group VII ethylene response factors, which are primarily degraded through the oxygen-dependent Cys-Arg branch of the N-degron pathway of targeted proteolysis. Knockout of PRT6, an E3 ligase and a vital component of the N-degron pathway, improves submergence tolerance in Arabidopsis and barley but is associated with side effects such as germination deficiency. In this study, we determined structures of rice and Arabidopsis PRT6-UBR box in complex with various Arg/N-degron related peptides. We identified two highly conserved motifs in the plant PRT6-UBR box, which is responsible for Cys-Arg/N-degron recognition. Structural and mutagenesis studies revealed the importance of two conserved motifs for Cys-Arg/N-degron recognition. The phenotype of Arabidopsis seedlings with PRT6-UBR mutants in these newly identified conserved motifs showed superior submergence survival suggesting that rational manipulation of the PRT6-UBR box can improve flood tolerance. Our results provide an engineering platform for generating crops with improved submergence tolerance.

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Section: Resultsmentioning

confidence: 99%

“…As described above, Asp can mimic CysO2 25,26 . Geometries of both the sulfinate (-SO2) and carboxylate (-CO2) groups are approximately trigonal planar, and the distance of the S-O bond is 0.1 Å longer than a C-O bond.…”

Section: Recognition Of the Second Position Of The Cys-arg/n-degron B...mentioning

confidence: 99%

Structural analyses of the plant PRT6-UBR box in the Cys-Arg/N-degron pathway and insights into the plant submergence response

Kim

Lin

et al. 2022

Preprint

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“…[9] Aβ has a native Zn 2+ binding site that binds the metal ion in a 1:1 ratio. A model peptide of Aβ with the sequence Ac-DAEFRHDSGYEVHHQK [5] (pAβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)) that contains a phosphorylated Ser was used to investigate the effect of this PTM. Probing the stoichiometry between Zn 2+ and pAβ(1-16) revealed the presence of two binding sites with stoichiometries of 1:1 and 1:0.5.…”

Section: Amyloid-βmentioning

confidence: 99%

“…In the non-modified peptide, the fragment EVHH binds one Zn 2+ ion in a first step, and His at position 6 closes the first coordination sphere. However, the same His in pAβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) is excluded from this binding site by forming the second binding site with pS8. Consequently, the first binding site is completed by residues from another phosphorylated peptide, rise to the dimerization event.…”

Section: Amyloid-βmentioning

confidence: 99%

“…Zondlo and Urney probed the effect of Cys oxidation to sulfinic acid (Cys-SO 2 -) on metal-binding in an EF-Hand motif and harnessed this PTM to develop it into a genetically encodable protein tag that is responsive to this particular Cys oxidative modification by giving rise to luminescence in the presence of Tb 3+ ions. [16] Short peptides were designed based on the Ca 2+ binding calmodulin (CaM) EF-Hand motif, which shows the response to Cys-SO 2 formation through enhanced Tb 3+ binding. Cys and Cys-SO 2 were systematically placed in the mimetic peptide Ac-DKDACGWISPAEAK-NH 2 .…”

Section: Detection Of Cys Oxidationmentioning

confidence: 99%

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Enhancing Metal-binding with Noncanonical Coordinating Amino Acids

Sauser

Shoshan

2021

Chimia

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More than 50% of proteinogenic amino acid sidechains can bind metal ions, enabling proteins and peptides to bear these ions as cofactors. Nevertheless, post-translational modifications and incorporation of noncanonical amino acids bestow peptides and proteins myriads of other coordination capabilities, thanks to an enhanced metal binding. Here we summarize selected examples of natural and artificial systems that contain one or more noncanonical amino acids coordinating a metal ion and subsequently achieve a new or enhanced function. We report on a wide array of systems: from disease-related proteins that undergo sulfurylation or phosphorylation through natural metallophores that selectively capture precious essential ions to synthetic selfassembly strategies, biocatalysts, and chelating agents against toxic metals. Regardless of their (bio)synthetic routes, all possess unique metal-binding properties that could not be effectively achieved by systems composed of canonical residues.

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