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Insights into the structure-function relationship of the NorQ/NorD chaperones from Paracoccus denitrificans reveal shared principles of interacting MoxR AAA+/VWA domain proteins
Open accessPreprint — published as 10.1186/s12915-023-01546-w · Paper page
Abstract
NorQ, a member of the MoxR-class of AAA+ ATPases, and NorD, a protein containing a Von Willebrand Factor Type A (VWA) domain, are essential for non-heme iron (Fe B ) cofactor insertion into cytochrome c -dependent nitric oxide reductase ( c NOR). c NOR catalyzes the NO reduction, a key step of bacterial denitrification. This work aimed at elucidating the specific mechanism of NorQD-catalyzed Fe B insertion, and the general mechanism of the MoxR/VWA interacting protein families. We show that NorQ-catalyzed ATP hydrolysis, an intact VWA-domain in NorD and specific surface carboxylates on c NOR are all features required for c NOR activation. Supported by BN-PAGE, low-resolution cryo-EM structures of NorQ and the NorQD complex show that NorQ forms a circular hexamer with a monomer of NorD binding both to the side and to the central pore of the NorQ ring. Guided by AlphaFold predictions, we assign the density that ‘plugs’ the NorQ ring pore to the VWA domain of NorD with a protruding ‘finger’ inserting through the pore, and suggest this binding mode to be general for MoxR/VWA couples. We present a tentative model for the mechanism of NorQD-catalyzed c NOR remodelling and suggest many of its features to be applicable to the whole MoxR/VWA family.
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Metadata
- Authors
- Kahle, M., Appelgren, S., Elofsson, A., Carroni, M., & Ädelroth, P.
- Affiliations
- Stockholm University (SE)
- Corresponding author
- Kahle, Maximilian
- Carroni, Marta
- Ädelroth, Pia
- Venue
- BMC Biology
- Publisher
- openRxiv
- Published
- 2022-11-16
- Volume
- 21
- Issue
- 1
- Pages
- 47-47
- ISSN
- 1741-7007 (ISSN-L)
- PMC
- PMC9976466
- OpenAlex
- W4322625116
- Cited by
- 10
- References
- 1
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 1
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Kempe Foundation
- Swedish e-Science Research Centre
- Knut och Alice Wallenbergs Stiftelse
- Universität Potsdam
- Vetenskapsrådet (2015-04512, 2016-06301, 2019-04124, Berzelius-2021-29)
- Kempestiftelserna
- Stockholms Universitet
- Science for Life Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Metalloenzymes and iron-sulfur proteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- Nord, VWA domain, Paracoccus denitrificans, denitrification, ATP hydrolysis, protein complex structure, structure-function relationship, molecular chaperones
- MeSH terms
- AAA Proteins, Norethindrone, Paracoccus denitrificans, Structure-Activity Relationship, Molecular Chaperones
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