title: Structure and dynamics of a compact state of a multidomain protein, the mercuric ion reductase.
abstract: The functional efficacy of colocalized, linked protein domains is dependent on linker flexibility and system compaction. However, the detailed characterization of these properties in aqueous solution presents an enduring challenge. Here, we employ a novel, to our knowledge, combination of complementary techniques, including small-angle neutron scattering, neutron spin-echo spectroscopy, and all-atom molecular dynamics and coarse-grained simulation, to identify and characterize in detail the structure and dynamics of a compact form of mercuric ion reductase (MerA), an enzyme central to bacterial mercury resistance. MerA possesses metallochaperone-like N-terminal domains (NmerA) tethered to its catalytic core domain by linkers. The NmerA domains are found to interact principally through electrostatic interactions with the core, leashed by the linkers so as to subdiffuse on the surface over an area close to the core C-terminal Hg(II)-binding cysteines. How this compact, dynamical arrangement may facilitate delivery of Hg(II) from NmerA to the core domain is discussed.
authors.affiliation: Center for Molecular Biophysics, Oak Ridge National Laboratory, Tennessee; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee; Department of Physics and Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hong
authors.affiliation: European Spallation Source ESS AB, Lund, Sweden; Jülich Center of Neutron Science, Outstation at the Spallation Neutron Source (SNS), Oak Ridge, Tennessee.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Sharp
authors.affiliation: Institute of Complex Systems & Institute for Advanced Simulation, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Simón
authors.initials: S
authors.lastname: Poblete
authors.affiliation: Jülich Center of Neutron Science & Institute of Complex Systems, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Biehl
authors.affiliation: Jülich Centre for Neutron Science JCNS, Forschungszentrum Jülich GmbH Outstation at MLZ, Garching, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Zamponi
authors.affiliation: Jülich Centre for Neutron Science JCNS, Forschungszentrum Jülich GmbH Outstation at MLZ, Garching, Germany.
authors.forename: Noemi
authors.initials: N
authors.lastname: Szekely
authors.affiliation: Jülich Centre for Neutron Science JCNS, Forschungszentrum Jülich GmbH Outstation at MLZ, Garching, Germany.
authors.forename: Marie-Sousai
authors.initials: MS
authors.lastname: Appavou
authors.affiliation: Institute of Complex Systems & Institute for Advanced Simulation, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Roland G
authors.initials: RG
authors.lastname: Winkler
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Nauss
authors.affiliation: Environmental Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
authors.forename: Alexander
authors.initials: A
authors.lastname: Johs
authors.affiliation: Center for Molecular Biophysics, Oak Ridge National Laboratory, Tennessee.
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Parks
authors.affiliation: Center for Molecular Biophysics, Oak Ridge National Laboratory, Tennessee; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Center for Molecular Biophysics, Oak Ridge National Laboratory, Tennessee.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Environmental Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Liang
authors.affiliation: Jülich Centre for Neutron Science JCNS, Forschungszentrum Jülich GmbH Outstation at MLZ, Garching, Germany. Electronic address: m.ohl@fz-juelich.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Ohl
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California. Electronic address: smiller@cgl.ucsf.edu.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Miller
authors.affiliation: Jülich Center of Neutron Science & Institute of Complex Systems, Forschungszentrum Jülich, Jülich, Germany. Electronic address: d.richter@fz-juelich.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Richter
authors.affiliation: Institute of Complex Systems & Institute for Advanced Simulation, Forschungszentrum Jülich, Jülich, Germany. Electronic address: g.gompper@fz-juelich.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gompper
authors.affiliation: Center for Molecular Biophysics, Oak Ridge National Laboratory, Tennessee; Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee. Electronic address: smithjc@ornl.gov.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D008969:Molecular Sequence Data; D033363:Neutron Diffraction; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D053838:Scattering, Small Angle; D055672:Static Electricity
chemical_list: D010088:Oxidoreductases; C021551:mercuric reductase