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PDBsum entry 2iqc
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Protein binding
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PDB id
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2iqc
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References listed in PDB file
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Key reference
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Title
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Structural determinants of human fancf protein that function in the assembly of a DNA damage signaling complex.
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Authors
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P.Kowal,
A.M.Gurtan,
P.Stuckert,
A.D.D'Andrea,
T.Ellenberger.
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Ref.
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J Biol Chem, 2007,
282,
2047-2055.
[DOI no: ]
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PubMed id
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Abstract
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Fanconi anemia (FA) is a rare autosomal recessive and X-linked chromosomal
instability disorder. At least eight FA proteins (FANCA, B, C, E, F, G, L, and
M) form a nuclear core complex required for monoubiquitination of a downstream
protein, FANCD2. The human FANCF protein reportedly functions as a molecular
adaptor within the FA nuclear complex, bridging between the subcomplexes A:G and
C:E. Our x-ray crystallographic studies of the C-terminal domain of FANCF reveal
a helical repeat structure similar to the Cand1 regulator of the
Cul1-Rbx1-Skp1-Fbox(Skp2) ubiquitin ligase complex. Two C-terminal loops of
FANCF are essential for monoubiquitination of FANCD2 and normal cellular
resistance to the DNA cross-linking agent mitomycin C. FANCF mutants bearing
amino acid substitutions in this C-terminal surface fail to interact with other
components of the FA complex, indicating that this surface is critical for the
proper assembly of the FA core complex.
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Figure 1.
FIGURE 1. Overall fold and surface representation of the
CTD of FANCF. a, the protein fold of the CTD of the FANCF
fragment consists of 10  -helices. Helices 2- 9 form
four hairpins (HP1-HP4) flanked on the N and C termini by helix
1
(purple) and 10 (red), respectively.
Loop L1, connecting helix 1 and 2 of
hairpin HP1 and loop L2, connecting helix 3 of HP1 with helix
4
of hairpin HP2 are disordered in the crystals. b, full-length
human FANCF (gray bar) is a 374-residue polypeptide. The
crystallized fragment includes residues 156-357 (green bar). A
region of high sequence conservation (Leu-329-Leu-352, orange)
is expanded to show alignment between four species (Fr, Fugu
rubripes; Xl, Xenopus laevis; Mm, Mus musculus; and Hs, Homo
sapiens). c, surface representations of FANCF CTD showing the
location of the Leu-329-Leu-352 conserved region (orange).
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Figure 7.
FIGURE 7. Human FANCF protein mediates the assembly of the
FA complex via its N and C termini. FANCF may bind to the
preassembled FANCA: FANCG and FANCC:FANCE subcomplexes through
its CTD and N-terminal domain, respectively (Ref. 33 and this
study). Both interactions are necessary to stabilize the FA core
nuclear complex, probably by apposing the FANCC: FANCE and
FANCA:FANCG subcomplexes to facilitate additional interactions
that configure the protein complex for monoubiquitination of
FANCD2.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
2047-2055)
copyright 2007.
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