AsIII Selectively Induces a Disorder-to-Order Transition in the Metalloid Binding Region of the AfArsR Protein
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AsIII Selectively Induces a Disorder-to-Order Transition in the Metalloid Binding Region of the AfArsR Protein. / Tóth, Annamária; Sajdik, Kadosa; Gyurcsik, Béla; Nafaee, Zeyad H.; Wéber, Edit; Kele, Zoltan; Christensen, Niels Johan; Schell, Juliana; Correia, Joao Guilherme; Sigfridsson Clauss, Kajsa G.V.; Pittkowski, Rebecca K.; Thulstrup, Peter Waaben; Hemmingsen, Lars; Jancsó, Attila.
I: Journal of the American Chemical Society, Bind 146, Nr. 25, 2024, s. 17009-17022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - AsIII Selectively Induces a Disorder-to-Order Transition in the Metalloid Binding Region of the AfArsR Protein
AU - Tóth, Annamária
AU - Sajdik, Kadosa
AU - Gyurcsik, Béla
AU - Nafaee, Zeyad H.
AU - Wéber, Edit
AU - Kele, Zoltan
AU - Christensen, Niels Johan
AU - Schell, Juliana
AU - Correia, Joao Guilherme
AU - Sigfridsson Clauss, Kajsa G.V.
AU - Pittkowski, Rebecca K.
AU - Thulstrup, Peter Waaben
AU - Hemmingsen, Lars
AU - Jancsó, Attila
N1 - Funding Information: The authors acknowledge the financial support received from the German Ministry of Education and Research (BMBF) under Grants 05K16PGA, 05K22PGA, and 05K22PGB, the Portuguese Foundation for Science and Technology (FCT, Projects CERN/FIS-TEC/0003/2019 and CERN/FIS-TEC/0003/2021), and from the European Union\u2019s Horizon 2020 Framework Research and Innovation Program under Grant Agreement No. 654002 (ENSAR2). The authors thank CERN and the ISOLDE technical team for beam time as well as EURONS and NICE for financial support. The authors acknowledge MAX IV Laboratory for time on Beamline Balder under Proposal 20240082. Research conducted at MAX IV, a Swedish national user facility, is supported by the Swedish Research council under Contract 2018-07152, the Swedish Governmental Agency for Innovation Systems under Contract 2018-04969, and Formas under Contract 2019-02496. N.J.C. is grateful for the research grant 40932 awarded by VILLUM FONDEN, and Z.H.N. acknowledges support from the College of Pharmacy, University of Babylon, Hillah 51001, Iraq. Publisher Copyright: © 2024 American Chemical Society.
PY - 2024
Y1 - 2024
N2 - Arsenic is highly toxic and a significant threat to human health, but certain bacteria have developed defense mechanisms initiated by AsIII binding to AsIII-sensing proteins of the ArsR family. The transcriptional regulator AfArsR responds to AsIII and SbIII by coordinating the metalloids with three cysteines, located in a short sequence of the same monomer chain. Here, we characterize the binding of AsIII and HgII to a model peptide encompassing this fragment of the protein via solution equilibrium and spectroscopic/spectrometric techniques (pH potentiometry, UV, CD, NMR, PAC, EXAFS, and ESI-MS) combined with DFT calculations and MD simulations. Coordination of AsIII changes the peptide structure from a random-coil to a well-defined structure of the complex. A trigonal pyramidal AsS3 binding site is formed with almost exactly the same structure as observed in the crystal structure of the native protein, implying that the peptide possesses all of the features required to mimic the AsIII recognition and response selectivity of AfArsR. Contrary to this, binding of HgII to the peptide does not lead to a well-defined structure of the peptide, and the atoms near the metal binding site are displaced and reoriented in the HgII model. Our model study suggests that structural organization of the metal site by the inducer ion is a key element in the mechanism of the metalloid-selective recognition of this protein.
AB - Arsenic is highly toxic and a significant threat to human health, but certain bacteria have developed defense mechanisms initiated by AsIII binding to AsIII-sensing proteins of the ArsR family. The transcriptional regulator AfArsR responds to AsIII and SbIII by coordinating the metalloids with three cysteines, located in a short sequence of the same monomer chain. Here, we characterize the binding of AsIII and HgII to a model peptide encompassing this fragment of the protein via solution equilibrium and spectroscopic/spectrometric techniques (pH potentiometry, UV, CD, NMR, PAC, EXAFS, and ESI-MS) combined with DFT calculations and MD simulations. Coordination of AsIII changes the peptide structure from a random-coil to a well-defined structure of the complex. A trigonal pyramidal AsS3 binding site is formed with almost exactly the same structure as observed in the crystal structure of the native protein, implying that the peptide possesses all of the features required to mimic the AsIII recognition and response selectivity of AfArsR. Contrary to this, binding of HgII to the peptide does not lead to a well-defined structure of the peptide, and the atoms near the metal binding site are displaced and reoriented in the HgII model. Our model study suggests that structural organization of the metal site by the inducer ion is a key element in the mechanism of the metalloid-selective recognition of this protein.
U2 - 10.1021/jacs.3c11665
DO - 10.1021/jacs.3c11665
M3 - Journal article
C2 - 38820242
AN - SCOPUS:85195038891
VL - 146
SP - 17009
EP - 17022
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 25
ER -
ID: 395086832