title: The solution structure of apo-iron regulatory protein 1.
abstract: Iron is a cofactor for many proteins that are involved in essential metabolic processes. However, iron must be strictly regulated because it can react with oxygen to generate cytotoxic reactive oxygen intermediates. Iron regulatory protein 1 (IRP1) is a bi-functional protein that can act either as a post-transcriptional regulator of mRNAs containing iron responsive elements, or as a [4Fe-4S] cluster-containing cytosolic aconitase. Previous X-ray crystallography results show that IRP1 is in an open L-shape conformation when bound to IRE-RNAs, and in a globular conformation when it binds an iron-sulfur cluster. The structure of apo-IRP1 and the mechanism by which it transforms to either functional state is unknown. Therefore, small angle X-ray scattering was used to determine the low resolution solution structure of apo-IRP1 and to characterize its biophysical properties. These results show that apo-IRP1 has a radius of gyration (Rg) of 33.6±0.3Å, and a Dmax of 118±2Å. The ab initio and rigid-body modeling results show that apo-IRP1 is in an open conformation in solution, and the ensemble optimization results show that the molecules stay narrowly distributed about a Rg of 33-34Å. The open apo-IRP1 conformation seems optimal for subsequent conversion to either functional end state: RNA-binding, or cytosolic aconitase.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612, USA. oshand2@uic.edu
authors.forename: O'Neil
authors.initials: O
authors.lastname: Shand
authors.forename: Karl
authors.initials: K
authors.lastname: Volz
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000737:chemistry; D035941:Iron Regulatory Protein 1 / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D016601:RNA-Binding Proteins / Q000737:chemistry*; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D053838:Scattering, Small Angle; D012996:Solutions / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D001053:Apolipoproteins; D016601:RNA-Binding Proteins; D012996:Solutions; D012313:RNA; D035941:Iron Regulatory Protein 1