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Biomolecules 2014, 4(2), 474-497; doi:10.3390/biom4020474
Review

The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase

1
,
2
 and
1,*
1 Laboratory of Biochemistry, Department of Pathology, University of Pisa, via Roma 55, Pisa 56126, Italy 2 Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2UH, UK
* Author to whom correspondence should be addressed.
Received: 6 February 2014 / Revised: 8 April 2014 / Accepted: 10 April 2014 / Published: 5 May 2014
(This article belongs to the Special Issue Metal Binding Proteins)
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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.
Keywords: AMP deaminase; histidine-proline-rich glycoprotein; zinc chaperone; zinc binding site AMP deaminase; histidine-proline-rich glycoprotein; zinc chaperone; zinc binding site
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Ranieri-Raggi, M.; Moir, A.J.G.; Raggi, A. The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase. Biomolecules 2014, 4, 474-497.

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