title: The role of histidine-proline-rich glycoprotein as zinc chaperone for skeletal muscle AMP deaminase.
abstract: Metallochaperones function as intracellular shuttles for metal ions. At present, no evidence for the existence of any eukaryotic zinc-chaperone has been provided although metallochaperones could be critical for the physiological functions of Zn2+ metalloenzymes. We propose that the complex formed in skeletal muscle by the Zn2+ metalloenzyme AMP deaminase (AMPD) and the metal binding protein histidine-proline-rich glycoprotein (HPRG) acts in this manner. HPRG is a major plasma protein. Recent investigations have reported that skeletal muscle cells do not synthesize HPRG but instead actively internalize plasma HPRG. X-ray absorption spectroscopy (XAS) performed on fresh preparations of rabbit skeletal muscle AMPD provided evidence for a dinuclear zinc site in the enzyme compatible with a (μ-aqua)(μ-carboxylato)dizinc(II) core with two histidine residues at each metal site. XAS on HPRG isolated from the AMPD complex showed that zinc is bound to the protein in a dinuclear cluster where each Zn2+ ion is coordinated by three histidine and one heavier ligand, likely sulfur from cysteine. We describe the existence in mammalian HPRG of a specific zinc binding site distinct from the His-Pro-rich region. The participation of HPRG in the assembly and maintenance of skeletal muscle AMPD by acting as a zinc chaperone is also demonstrated.
authors: Laboratory of Biochemistry, Department of Pathology, University of Pisa, via Roma 55, Pisa 56126, Italy. maria.ranieri@med.unipi.it.
authors: Maria
authors: M
authors: Ranieri-Raggi
authors: Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2UH, UK. a.j.moir@sheffield.ac.uk.
authors: Arthur J G
authors: AJ
authors: Moir
authors: Laboratory of Biochemistry, Department of Pathology, University of Pisa, via Roma 55, Pisa 56126, Italy. antonio.raggi@med.unipi.it.
authors: Antonio
authors: A
authors: Raggi
mesh_terms: D000659:AMP Deaminase / Q000378:metabolism*; D000818:Animals; D006801:Humans; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*; D000099053:Histidine-Rich Glycoprotein
chemical_list: D018832:Molecular Chaperones; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; D000659:AMP Deaminase; D015032:Zinc