Structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states

Maciunas, Lina J.; Porter, Nadia; Lee, Paula J.; Gupta, Kushol; Loll, Patrick J.

doi:10.1107/s2059798321006288

Title: Structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states

Journal Article · 28 July 2021 · Acta Crystallographica. Section D. Structural Biology

DOI: https://doi.org/10.1107/s2059798321006288 · OSTI ID:1879694

Maciunas, Lina J. ^[1]; Porter, Nadia ^[1]; Lee, Paula J. ^[1]; Gupta, Kushol ^[2]; Loll, Patrick J. ^[1]

Drexel University College of Medicine, Philadelphia, PA (United States)
Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine

Vancomycin has historically been used as a last-resort treatment for serious bacterial infections. However, vancomycin resistance has become widespread in certain pathogens, presenting a serious threat to public health. Resistance to vancomycin is conferred by a suite of resistance genes, the expression of which is controlled by the VanR–VanS two-component system. VanR is the response regulator in this system; in the presence of vancomycin, VanR accepts a phosphoryl group from VanS, thereby activating VanR as a transcription factor and inducing expression of the resistance genes. This paper presents the X-ray crystal structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states at resolutions of 2.3 and 2.0 Å, respectively. Comparison of the two structures illustrates that phosphorylation of VanR is accompanied by a disorder-to-order transition of helix 4, which lies within the receiver domain of the protein. This transition generates an interface that promotes dimerization of the receiver domain; dimerization in solution was verified using analytical ultracentrifugation. The inactive conformation of the protein does not appear intrinsically unable to bind DNA; rather, it is proposed that in the activated form DNA binding is enhanced by an avidity effect contributed by the receiver-domain dimerization.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357; SC0012704

OSTI ID:: 1879694

Journal Information:: Acta Crystallographica. Section D. Structural Biology, Journal Name: Acta Crystallographica. Section D. Structural Biology Journal Issue: 8 Vol. 77; ISSN 2059-7983

Publisher:: International Union of CrystallographyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES
full-length VanR
response regulators
streptomyces coelicolor
two-component systems
vancomycin resistance
x-ray crystallography

Title: Structures of full-length VanR from Streptomyces coelicolor in both the inactive and activated states

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