title: Mapping ultra-weak protein-protein interactions between heme transporters of Staphylococcus aureus.
abstract: Iron is an essential nutrient for the proliferation of Staphylococcus aureus during bacterial infections. The iron-regulated surface determinant (Isd) system of S. aureus transports and metabolizes iron porphyrin (heme) captured from the host organism. Transportation of heme across the thick cell wall of this bacterium requires multiple relay points. The mechanism by which heme is physically transferred between Isd transporters is largely unknown because of the transient nature of the interactions involved. Herein, we show that the IsdC transporter not only passes heme ligand to another class of Isd transporter, as previously known, but can also perform self-transfer reactions. IsdA shows a similar ability. A genetically encoded photoreactive probe was used to survey the regions of IsdC involved in self-dimerization. We propose an updated model that explicitly considers self-transfer reactions to explain heme delivery across the cell wall. An analogous photo-cross-linking strategy was employed to map transient interactions between IsdC and IsdE transporters. These experiments identified a key structural element involved in the rapid and specific transfer of heme from IsdC to IsdE. The resulting structural model was validated with a chimeric version of the homologous transporter IsdA. Overall, our results show that the ultra-weak interactions between Isd transporters are governed by bona fide protein structural motifs.
authors.affiliation: Department of Medical Genome Sciences, School of Frontier Sciences, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Abe
authors.forename: Jose M M
authors.initials: JM
authors.lastname: Caaveiro
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kozuka-Hata
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oyama
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
mesh_terms: D020816:Amino Acid Motifs; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006418:Heme / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D002352:Carrier Proteins; C512791:IsdA protein, Staphylococcus aureus; C488727:IsdC protein, Staphylococcus aureus; C488728:IsdE protein, Staphylococcus aureus; D006418:Heme