Cited by 93DNA Repair MechanismsEnzyme Structure and FunctionProtein Structure and Dynamics

The Structure of the Human Centrin 2-Xeroderma Pigmentosum Group C Protein Complex

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Thompson, James R., Ryan, Zachary C., Salisbury, Jeffrey L., Kumar, Rajiv·2006·Journal of Biological Chemistry

Abstract

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

  1. 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.
  2. Lingle, W. L., Lutz, W. H., Ingle, J. N., Maihle, N. J., and Salisbury, J. L. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 2950 -2955
  3. 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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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
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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