Mapping ultra-weak protein-protein interactions between heme transporters of Staphylococcus aureus

Ryota Abe, Jose M.M. Caaveiro, Hiroko Kozuka-Hata, Masaaki Oyama, Kouhei Tsumoto

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)16477-16487
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number20
DOIs
Publication statusPublished - May 11 2012
Externally publishedYes

Fingerprint

Heme
Staphylococcus aureus
Iron
Proteins
Cell Wall
Cells
Amino Acid Motifs
Dimerization
Structural Models
Porphyrins
Bacterial Infections
Nutrients
Bacteria
Ligands
Food
Experiments

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mapping ultra-weak protein-protein interactions between heme transporters of Staphylococcus aureus. / Abe, Ryota; Caaveiro, Jose M.M.; Kozuka-Hata, Hiroko; Oyama, Masaaki; Tsumoto, Kouhei.

In: Journal of Biological Chemistry, Vol. 287, No. 20, 11.05.2012, p. 16477-16487.

Research output: Contribution to journalArticle

Abe, Ryota ; Caaveiro, Jose M.M. ; Kozuka-Hata, Hiroko ; Oyama, Masaaki ; Tsumoto, Kouhei. / Mapping ultra-weak protein-protein interactions between heme transporters of Staphylococcus aureus. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 20. pp. 16477-16487.
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