Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor.
Pirin is a newly identified nuclear protein that interacts with the oncoprotein B-cell lymphoma 3-encoded (Bcl-3) and nuclear factor I (NFI). The crystal structure of human Pirin at 2.1-A resolution shows it to be a member of the functionally diverse cupin superfamily. The structure comprises two beta-barrel domains, with an Fe(II) cofactor bound within the cavity of the N-terminal domain. These findings suggest an enzymatic role for Pirin, most likely in biological redox reactions involving oxygen, and provide compelling evidence that Pirin requires the participation of the metal ion for its interaction with Bcl-3 to co-regulate the NF-kappaB transcription pathway and the interaction with NFI in DNA replication. Substitution of iron by heavy metals thus provides a novel pathway for these metals to directly influence gene transcription. The structure suggests an interesting new role of iron in biology and that Pirin may be involved in novel mechanisms of gene regulation.
Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China.
Hai
H
Pang
Mark
M
Bartlam
Qinghong
Q
Zeng
Hideyuki
H
Miyatake
Tamao
T
Hisano
Kunio
K
Miki
Luet-Lok
LL
Wong
George F
GF
Gao
Zihe
Z
Rao
D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D002467:Cell Nucleus / Q000378:metabolism*; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000378:metabolism; D049308:Dioxygenases; D015723:Gene Library; D006801:Humans; D007477:Ions; D033862:Iron-Binding Proteins / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008670:Metals / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry*; D010100:Oxygen / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D014158:Transcription, Genetic
D002352:Carrier Proteins; D018076:DNA, Complementary; D007477:Ions; D033862:Iron-Binding Proteins; D008670:Metals; D016328:NF-kappa B; D009687:Nuclear Proteins; D049308:Dioxygenases; C105340:PIR protein, human; D010100:Oxygen