4GUL

Study on structure and function relationships in human ferric Pirin

Summary for 4GUL

• Entry DOI: 10.2210/pdb4gul/pdb
• Related: 4ERO 4EWA 4EWD 4EWE 4HLT
• Descriptor: Pirin, FE (III) ION (3 entities in total)
• Functional Keywords: beta sandwich, cupin, iron, metal binding protein, transcription cofactor activity, protein binding, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : O00625
• Total number of polymer chains: 1
• Total formula weight: 32026.99

Authors

Liu, F.,Rehmani, I.,Fu, R.,Esaka, S.,Chen, L.,Serrano, V.,Liu, A. (deposition date: 2012-08-29, release date: 2013-05-29, Last modification date: 2023-09-13)

Primary citation

Liu, F.,Rehmani, I.,Esaki, S.,Fu, R.,Chen, L.,de Serrano, V.,Liu, A.
Pirin is an iron-dependent redox regulator of NF-kappa B.
Proc.Natl.Acad.Sci.USA, 110:9722-9727, 2013

PubMed Abstract: Pirin is a nuclear nonheme Fe protein of unknown function present in all human tissues. Here we describe that pirin may act as a redox sensor for the nuclear factor κB (NF-κB) transcription factor, a critical mediator of intracellular signaling that has been linked to cellular responses to proinflammatory signals and controls the expression of a vast array of genes involved in immune and stress responses. Pirin's regulatory effect was tested with several metals and at different oxidations states, and our spectroscopic results show that only the ferric form of pirin substantially facilitates binding of NF-κB proteins to target κB genes, a finding that suggests that pirin performs a redox-sensing role in NF-κB regulation. The molecular mechanism of such a metal identity- and redox state-dependent regulation is revealed by our structural studies of pirin. The ferrous and ferric pirin proteins differ only by one electron, yet they have distinct conformations. The Fe center is shown to play an allosteric role on an R-shaped surface area that has two distinct conformations based on the identity and the formal redox state of the metal. We show that the R-shaped area composes the interface for pirin-NF-κB binding that is responsible for modulation of NF-κB's DNA-binding properties. The nonheme Fe protein pirin is proposed to serve as a reversible functional switch that enables NF-κB to respond to changes in the redox levels of the cell nucleus.

PubMed: 23716661
DOI: 10.1073/pnas.1221743110

Experimental method

X-RAY DIFFRACTION (1.8 Å)