The radical SAM protein HemW is a heme chaperone - Aix-Marseille Université Access content directly
Journal Articles Journal of Biological Chemistry Year : 2018

The radical SAM protein HemW is a heme chaperone

Vera Haskamp
  • Function : Author
Simone Karrie
  • Function : Author
Toni Mingers
  • Function : Author
Stefan Barthels
  • Function : Author
François Alberge
  • Function : Author
  • PersonId : 1347782
  • IdHAL : falberge
Axel Magalon
Katrin Müller
  • Function : Author
Kirstin Kleeberg
  • Function : Author
Peter Schweyen
  • Function : Author
Martin Bröring
  • Function : Author
  • PersonId : 886760


Radical S-adenosylmethionine (SAM) enzymes exist in organisms from all kingdoms of life, and all of these proteins generate an adenosyl radical via the homolytic cleavage of the S–C(5’) bond of SAM. Of particular interest are radical SAM enzymes, such as heme chaperones, that insert heme into respiratory enzymes. For example, heme chaperones insert heme into target proteins, but have been studied only for the formation of cytochrome c type hemoproteins. Here, we report that a radical SAM protein, the heme chaperone HemW from bacteria, is required for the insertion of heme b into respiratory chain enzymes. As other radical SAM proteins, HemW contains three cysteines and one SAM coordinating an [4Fe-4S] cluster, and we observed one heme per subunit of HemW. We found that an intact iron-sulfur cluster was required for HemW dimerization and HemW-catalyzed heme transfer, but not for stable heme binding. A bacterial two-hybrid system screen identified bacterioferritins and the heme-containing subunit NarI of the respiratory nitrate reductase NarGHI as proteins that interact with HemW. We also noted that the bacterioferritins potentially serve as heme donors for HemW. Of note, heme that was covalently bound to HemW was actively transferred to a heme-depleted, catalytically inactive nitrate reductase, restoring its nitrate-reducing enzyme activity. Finally, the human HemW orthologue radical SAM domain– containing 1 (RSAD1) stably bound heme. In conclusion, our findings indicate that the radicalSAM protein family HemW/RSAD1 is a heme chaperone catalyzing the insertion ofheme into hemoproteins.
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Dates and versions

hal-01915476 , version 1 (09-11-2018)





Vera Haskamp, Simone Karrie, Toni Mingers, Stefan Barthels, François Alberge, et al.. The radical SAM protein HemW is a heme chaperone. Journal of Biological Chemistry, 2018, 293 (7), pp.2558 - 2572. ⟨10.1074/jbc.RA117.000229⟩. ⟨hal-01915476⟩


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