Architecture of the membrane-bound cytochrome c heme lyase CcmF
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The covalent attachment of one or multiple heme cofactors to cytochrome c protein chains enables cytochrome c proteins to be used in electron transfer and redox catalysis in extracytoplasmic environments. A dedicated heme maturation machinery, whose core component is a heme lyase, scans nascent peptides after Sec-dependent translocation for CX n CH-binding motifs. Here we report the three-dimensional (3D) structure of the heme lyase CcmF, a 643-amino acid integral membrane protein, from Thermus thermophilus. CcmF contains a heme b cofactor at the bottom of a large cavity that opens toward the extracellular side to receive heme groups from the heme chaperone CcmE for cytochrome maturation. A surface groove on CcmF may guide the extended apoprotein to heme attachment at or near a loop containing the functionally essential WXWD motif, which is situated above the putative cofactor binding pocket. The structure suggests heme delivery from within the membrane, redefining the role of the chaperone CcmE.
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TM-heme was co-crystallized with CcmF from Thermus thermophilus (TtCcmF) in a recent published X-ray structure.
“TM-heme was co-crystallized with CcmF from Thermus thermophilus (TtCcmF) in a recent published X-ray structure49.”
From AF2Complex predicts direct physical interactions in multimeric proteins with deep learning (2022) · cites this paper as [49]
CcmF in our model does not expose a pore as observed in the TtCcmF structure, in which the pore was speculated to enable P-heme access.
“CcmF in our model does not expose a pore as observed in the TtCcmF structure, in which the pore was speculated to enable P-heme access49.”
From AF2Complex predicts direct physical interactions in multimeric proteins with deep learning (2022) · cites this paper as [49]
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AF2Complex predicts direct physical interactions in multimeric proteins with deep learning
Gao, M., Nakajima An, D., Parks, J. M., & Skolnick, J. (2022) · Nature Communications · doi:10.1038/s41467-022-29394-2 · Cited by 252 · see citing works
- Authors
- Brausemann, A., Zhang, L., Ilcu, L., & Einsle, O.
- Affiliations
- University of Freiburg (DE)
- Corresponding author
- Einsle, Oliver
- Venue
- Nature Chemical Biology
- Published
- 2021-05-06
- Volume
- 17
- Issue
- 7
- Pages
- 800-805
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC7611092
- OpenAlex
- W3159136559
- Cited by
- 29
- References
- 57
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 3 · 2021: 4
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Topics
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- cytochrome c maturation, heme attachment, integral membrane proteins, Thermus thermophilus, protein structure
- MeSH terms
- Cell Membrane, Lyases, Thermus thermophilus
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