title: Monothiol glutaredoxins and A-type proteins: partners in Fe-S cluster trafficking.
abstract: Monothiol glutaredoxins (Grxs) are proposed to function in Fe-S cluster storage and delivery, based on their ability to exist as apo monomeric forms and dimeric forms containing a subunit-bridging [Fe(2)S(2)](2+) cluster, and to accept [Fe(2)S(2)](2+) clusters from primary scaffold proteins. In addition yeast cytosolic monothiol Grxs interact with Fra2 (Fe repressor of activation-2), to form a heterodimeric complex with a bound [Fe(2)S(2)](2+) cluster that plays a key role in iron sensing and regulation of iron homeostasis. In this work, we report on in vitro UV-visible CD studies of cluster transfer between homodimeric monothiol Grxs and members of the ubiquitous A-type class of Fe-S cluster carrier proteins ((Nif)IscA and SufA). The results reveal rapid, unidirectional, intact and quantitative cluster transfer from the [Fe(2)S(2)](2+) cluster-bound forms of A. thaliana GrxS14, S. cerevisiae Grx3, and A. vinelandii Grx-nif homodimers to A. vinelandii(Nif)IscA and from A. thaliana GrxS14 to A. thaliana SufA1. Coupled with in vivo evidence for interaction between monothiol Grxs and A-type Fe-S cluster carrier proteins, the results indicate that these two classes of proteins work together in cellular Fe-S cluster trafficking. However, cluster transfer is reversed in the presence of Fra2, since the [Fe(2)S(2)](2+) cluster-bound heterodimeric Grx3-Fra2 complex can be formed by intact [Fe(2)S(2)](2+) cluster transfer from (Nif)IscA. The significance of these results for Fe-S cluster biogenesis or repair and the cellular regulation of the Fe-S cluster status are discussed.
authors.affiliation: Department of Chemistry and Center for Metalloenzyme Studies, University of Georgia, Athens, Georgia 30602, USA.
authors.forename: Daphne T
authors.initials: DT
authors.lastname: Mapolelo
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Sajini
authors.initials: S
authors.lastname: Randeniya
authors.forename: Angela-Nadia
authors.initials: AN
authors.lastname: Albetel
authors.forename: Haoran
authors.initials: H
authors.lastname: Li
authors.forename: Jérémy
authors.initials: J
authors.lastname: Couturier
authors.forename: Caryn E
authors.initials: CE
authors.lastname: Outten
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rouhier
authors.forename: Michael K
authors.initials: MK
authors.lastname: Johnson
mesh_terms: D016948:Azotobacter vinelandii; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D054477:Glutaredoxins / Q000737:chemistry* / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013455:Sulfur / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D054477:Glutaredoxins; D013438:Sulfhydryl Compounds; D013455:Sulfur; D007501:Iron