PDBsum entry 2iqc

Protein binding

PDB id: 2iqc

Contents

Protein chain

173 a.a.

Metals

_HG

Waters ×81

PDB id:

2iqc

Name:

Protein binding

Title:

Crystal structure of human fancf protein that functions in the assembly of a DNA damage signaling complex

Structure:

Fanconi anemia group f protein. Chain: a. Fragment: residues 156-357. Synonym: protein facf. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fancf. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.40Å R-factor: 0.196 R-free: 0.255

Authors:

P.Kowal,A.M.Gurtan,P.Stuckert,C.Lehmann,A.D'Andrea,T.E.Ellenberger

Key ref:

P.Kowal et al. (2007). Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex. J Biol Chem, 282, 2047-2055. PubMed id: 17082180 DOI: 10.1074/jbc.M608356200

Date:

13-Oct-06 Release date: 07-Nov-06

Protein chain

Q9NPI8  (FANCF_HUMAN) -  Fanconi anemia group F protein from Homo sapiens

Seq: 374 a.a.

Struc: 173 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M608356200

J Biol Chem 282:2047-2055 (2007)

PubMed id: 17082180

Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex.

P.Kowal, A.M.Gurtan, P.Stuckert, A.D.D'Andrea, T.Ellenberger.

ABSTRACT

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.

Selected figure(s)

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).

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.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 2047-2055) copyright 2007.

Figures were selected by an automated process.