title: The ATP/metallothionein interaction: NMR and STM.
abstract: We have previously established that ATP binds to mammalian metallothionein-2 (MT). The interaction between ATP and MT and the associated conformational change of the protein affect the sulfhydryl reactivity and zinc transfer potential of MT [Jiang, L.-J., Maret, W., and Vallee, B. L. (1998) The ATP-metallothionein complex. Proc. Natl. Acad. Sci. U.S.A. 95, 9146-9149]. NMR spectroscopic investigations have now provided further evidence for the interaction. (35)Cl NMR spectroscopy has further identified chloride as an additional biological MT ligand, which can interfere with the interaction of ATP with MT. (1)H NMR/TOCSY spectra demonstrate that ATP binding affects the N- and C-terminal amino acids of the MT molecule. Scanning tunneling microscopy recorded images of single MT molecules in buffered solutions. Moreover, this technique demonstrates that the otherwise nearly linear MT molecule bends by about 20 degrees at its central hinge region between the domains in the presence of ATP. These results may bear on the development of mild obesity in MT null mice and the role of MT in the regulation of energy balance. The interaction suggests a mechanism for the cellular translocation, retention, and reactivity of the ATP*MT complex in the mitochondrial intermembrane space. Both MT and ATP are localized there, and MT and thionein alternately bind and release zinc, thereby affecting mitochondrial respiration.
authors.affiliation: Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Seeley G. Mudd Building, 250 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maret
authors.forename: Gregory
authors.initials: G
authors.lastname: Heffron
authors.forename: H Allen O
authors.initials: HA
authors.lastname: Hill
authors.forename: Dejana
authors.initials: D
authors.lastname: Djuricic
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Jiang
authors.forename: Bert L
authors.initials: BL
authors.lastname: Vallee
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002021:Buffers; D002104:Cadmium / Q000737:chemistry; D002713:Chlorine; D008024:Ligands; D008668:Metallothionein / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D016252:Microscopy, Scanning Tunneling / Q000379:methods; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011522:Protons; D011817:Rabbits; D012996:Solutions
chemical_list: D002021:Buffers; D008024:Ligands; D011522:Protons; D012996:Solutions; D002104:Cadmium; D002713:Chlorine; D000255:Adenosine Triphosphate; D008668:Metallothionein