Cover image for Vol. 17 Issue 18

Editor: Meghan Campbell; Editorial Board Chairs: Thomas Carell, Donald Hilvert, Barbara Imperiali

Online ISSN: 1439-7633

Associated Title(s): ChemCatChem, ChemMedChem, ChemPhysChem, ChemSusChem

13_06/2012Cover Picture: The Structural Basis of Iron Sensing by the Human F-box Protein FBXL5 (ChemBioChem 6/2012)

The cover picture shows the structure of the di-iron center of a human F-box and leucine-rich repeat containing the protein FBXL5, a cytosolic iron and oxygen sensor that regulates the homeostasis of iron in vertebrates. FBXL5 mediates the ubiquitylation of the iron regulatory protein IRP2 through the SKP1-CUL1-FBXL5 (SCF) E3 ubiquitin ligase complex. High-resolution crystal structure revealed that the iron-binding domain of FBXL5 folds into a long helical bundle similar to the structure of invertebrate hemerythrin. The unique di-iron center structure and the flexibility of the protein allow FBXL5 to bind iron reversibly. Biophysical and structural studies showed that removal of the μ-hydroxo bridge in the di-iron center under reducing conditions facilitates the dissociation of the irons and unfolding of the protein. These insights into the structural basis of iron sensing by FBXL5 may be found in the communication by X. Tan, P. Li, et al. on p. 788 ff.

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