The Structure of the Human Centrin 2-Xeroderma Pigmentosum Group C Protein Complex
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Human centrin-2 plays a key role in centrosome function and stimulates nucleotide excision repair by binding to the xeroderma pigmentosum group C protein. To determine the structure of human centrin-2 and to develop an understanding of molecular interactions between centrin and xeroderma pigmentosum group C protein, we characterized the crystal structure of calcium-loaded full-length centrin-2 complexed with a xeroderma pigmentosum group C peptide. Our structure shows that the carboxyl-terminal domain of centrin-2 binds this peptide and two calcium atoms, whereas the amino-terminal lobe is in a closed conformation positioned distantly by an ordered alpha-helical linker. A stretch of the amino-terminal domain unique to centrins appears disordered. Two xeroderma pigmentosum group C peptides both bound to centrin-2 also interact to form an alpha-helical coiled-coil. The interface between centrin-2 and each peptide is predominantly nonpolar, and key hydrophobic residues of XPC have been identified that lead us to propose a novel binding motif for centrin.
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The long central helix observed in the Centrin2 (Rad33) structure is kinked about 90° in the Rad33-Rad14 complex model; both conformations are feasible and compatible for the interaction with Rad14.
“The long central helix observed in the Centrin2 (Rad33) structure (40) is kinked about 90° in our Rad33-Rad14 complex model (fig. S19B); both conformations are feasible and are compatible for the interaction with Rad14.”
From Computed structures of core eukaryotic protein complexes (2021) · cites this paper as [40]
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Research works printed but not linked: 3
- Lingle, W. L., Barrett, S. L., Negron, V. C., D'Assoro, A. B., Boeneman, K., Liu, W., Whitehead, C. M., Reynolds, C., and Salisbury, J. L. (2002) Proc. Natl. Acad. Sci.
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- Craig, T. A., Benson, L. M., Venyaminov, S. Y., Ryan, Z. C., Sperry, J., Thompson, J. R., Salisbury, J. L., Bergen, H. R., Gross, M. L., and Kumar, R. (2006) J. Am. Soc. Mass Spectrom., in press
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Computed structures of core eukaryotic protein complexes
Humphreys, I. R., Pei, J., Baek, M., Krishnakumar, A., Anishchenko, I., Ovchinnikov, S., Zhang, J., Ness, T. J., Banjade, S., Bagde, S. R., et al. (2021) · Science · doi:10.1126/science.abm4805 · Cited by 542 · see citing works
- Authors
- Thompson, J. R., Ryan, Z. C., Salisbury, J. L., & Kumar, R.
- Affiliations
- Mayo Clinic (US)
- University of Minnesota Rochester (US)
- Corresponding author
- Thompson, James R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 281
- Issue
- 27
- Pages
- 18746-18752
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2085261864
- Cited by
- 93
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 1 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 7 · 2012: 6
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-65830, R01DK065830, R21DK073369, DK 58546, R01DK058546)
- Brookhaven National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- centrin 2, XPC, nucleotide excision repair, centrosome, protein-protein interaction, crystal structure, calcium binding, C-terminal domain, coiled coil, DNA damage response
- MeSH terms
- Amino Acid Sequence, Binding Sites, Calcium, Calcium-Binding Proteins, DNA Repair, DNA-Binding Proteins, Humans, Models, Molecular, Molecular Sequence Data, Peptide Fragments, Protein Binding, Xeroderma Pigmentosum, Protein Structure, Tertiary, Cell Cycle Proteins, Amino Acid Motifs
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