Structures of two ArsR As(III)-responsive transcriptional repressors: Implications for the mechanism of derepression

Journal Article · Sat May 25 00:00:00 EDT 2019 · Journal of Structural Biology

DOI:https://doi.org/10.1016/j.jsb.2019.05.009· OSTI ID:1544840

Prabaharan, Chandrasekaran ^[1]; Kandavelu, Palani ^[2]; Packianathan, Charles ^[3]; Rosen, Barry P. ^[3]; Thiyagarajan, Saravanamuthu  ^[1]

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1. Inst. of Bioinformatics and Applied Biotechnology, Bengaluru, Karnataka (India)
2. Univ. of Georgia, Athens, GA (United States)
3. Florida International Univ., Miami, FL (United States). Herbert Wertheim College of Medicine

ArsR As(III)-responsive transcriptional repressors, members of the ArsR/SmtB family of metalloregulatory proteins, have been characterized biochemically but, to date, no As(III)-bound structure has been solved. Here in this paper we report two crystal structures of ArsR repressors from Acidithiobacillus ferrooxidans (AfArsR) and Corynebacterium glutamicum (CgArsR) in the As(III)-bound form. AfArsR crystallized in P21 space group and diffracted up to 1.86 Å. CgArsR crystallized in P212121 and diffracted up to 1.6 Å. AfArsR showed one As(III) bound in one subunit of the homodimer, while the CgArsR structure showed two As(III) bound with S3 coordination, one in each monomer. Previous studies indicated that in AfArsR As(III) binds to Cys95, Cys96 and Cys102 from the same monomer, while, in CgArsR, to Cys15, Cys16 from one monomer and Cys55 from the other monomer. The dimer interfaces of these structures showed distinct differences from other members of the ArsR/SmtB family of proteins, which potentially renders multiple options for evolving metal(loid) binding sites in this family of proteins. Also, CgArsR presents a new α2-N binding site, not the previously predicted α3-N site. Despite differences in the location of the binding cysteines in the primary sequences of these proteins, the two metal binding sites are almost congruent on their structures, an example of convergent evolution. Analyses of the electrostatic surface of the proteins at the DNA binding domain indicate that there two different modes of derepression in the ArsR/SmtB family of metalloregulatory proteins.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: Government of India; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES)
• Grant/Contract Number: GM55425; S10_RR25528; S10_RR028976; W-31-109-Eng-38
• OSTI ID: 1544840
• Journal Information: Journal of Structural Biology, Vol. 207, Issue 2; ISSN 1047-8477
• Publisher: Elsevier
• Country of Publication: United States
• Language: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES