title: A novel protein-mineral interface.
abstract: Transferrins transport Fe3+ and other metal ions in mononuclear-binding sites. We present the first evidence that a member of the transferrin superfamily is able to recognize multi-nuclear oxo-metal clusters, small mineral fragments that are the most abundant forms of many metals in the environment. We show that the ferric ion-binding protein from Neisseria gonorrhoeae (nFbp) readily binds clusters of Fe3+, Ti4+, Zr4+ or Hf4+ in solution. The 1.7 A resolution crystal structure of Hf-nFbp reveals three distinct types of clusters in an open, positively charged cleft between two hinged protein domains. A di-tyrosyl cluster nucleation motif (Tyr195-Tyr196) is situated at the bottom of this cleft and binds either a trinuclear oxo-Hf cluster, which is capped by phosphate, or a pentanuclear cluster, which in turn can be capped with phosphate. This first high-resolution structure of a protein-mineral interface suggests a novel metal-uptake mechanism and provides a model for protein-mediated mineralization/dissimilation, which plays a critical role in geochemical processes.
authors.affiliation: Institute of Cell and Molecular Biology, Michael Swann Building, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, UK.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Alexeev
authors.forename: Haizhong
authors.initials: H
authors.lastname: Zhu
authors.forename: Maolin
authors.initials: M
authors.lastname: Guo
authors.forename: Weiqing
authors.initials: W
authors.lastname: Zhong
authors.forename: Dominic J B
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Weiping
authors.initials: W
authors.lastname: Yang
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Campopiano
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001693:Biological Transport, Active; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006195:Hafnium / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D009344:Neisseria gonorrhoeae / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D008670:Metals; D011994:Recombinant Proteins; C471557:iron-transport protein, Neisseria gonorrhoeae; D007501:Iron; D006195:Hafnium