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PDBsum entry 2ggm
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References listed in PDB file
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Key reference
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Title
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The structure of the human centrin 2-Xeroderma pigmentosum group c protein complex.
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Authors
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J.R.Thompson,
Z.C.Ryan,
J.L.Salisbury,
R.Kumar.
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Ref.
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J Biol Chem, 2006,
281,
18746-18752.
[DOI no: ]
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PubMed id
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Abstract
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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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Figure 1.
FIGURE 1. Structure of human centrin-2 bound to a human
XPC-derived peptide. A, sequence of the HsCen-2 recognition site
from HsXPC structurally aligned with sequences of skeletal and
smooth muscle myosin light chain kinase (skMLCK and smMLCK) and
Kar1p from structures with calmodulin and yeast centrin (or
caltractin). The XPC peptide structure consists of residues
Asn^847-Arg^863, the HsXPC sequence underlined. Essential HsXPC
residues interacting to form  -helical coiled-coil
are indicated in red. Shaded pink are important HsXPC residues
interacting with HsCen-2. Positions numbered "1-5-8-14" of key
interfacial residues in skeletal muscle myosin light chain
kinase and smooth muscle myosin light chain kinase bound to
calmodulin are shown for comparison in purple. B, rainbow ribbon
trace of the main chains of HsCen-2 with HsXPC and two bound
Ca^2+ metals at the C-terminal domain. An ordered helical linker
separates N-terminal (blue)(Nterm) and C-terminal (red)(Cterm)
domains. The entire XPC peptide is -helix. C, two
complexes are found in the asymmetric unit. They interact solely
through bound XPC peptides that form an -helical coiled-coil
structure. D, the two independent complex structures are nearly
equivalent in overall conformation.
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Figure 3.
FIGURE 3. The two domains of HsCen-2 are compared. A
cross-eye stereo image is shown of a superposition of the
N-terminal HsCen-2 domain (blue) on the C-terminal domain (red).
The N-terminal domain exists in a closed conformation. Relative
positions of the two bound calcium atoms (dark green) bound to
EF-hands III and IV and the XPC peptide (green) with Trp^848,
Leu^851, and Leu^855 are drawn. The helices are numbered with
regard to past convention and Table 2 herein.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
18746-18752)
copyright 2006.
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