The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase
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...
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| Format: | Article |
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MDPI AG
2014-05-01
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| Series: | Biomolecules |
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| Online Access: | http://www.mdpi.com/2218-273X/4/2/474 |
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| author | Maria Ranieri-Raggi Arthur J. G. Moir Antonio Raggi |
| author_facet | Maria Ranieri-Raggi Arthur J. G. Moir Antonio Raggi |
| author_sort | Maria Ranieri-Raggi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T19:39:51Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-04-13T19:39:51Z |
| publishDate | 2014-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-2efe46a4af4a4e7db8b4bca114abafc62022-12-22T02:32:56ZengMDPI AGBiomolecules2218-273X2014-05-014247449710.3390/biom4020474biom4020474The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP DeaminaseMaria Ranieri-Raggi0Arthur J. G. Moir1Antonio Raggi2Laboratory of Biochemistry, Department of Pathology, University of Pisa, via Roma 55, Pisa 56126, ItalyDepartment of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield, Sheffield S10 2UH, UKLaboratory of Biochemistry, Department of Pathology, University of Pisa, via Roma 55, Pisa 56126, ItalyMetallochaperones 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.http://www.mdpi.com/2218-273X/4/2/474AMP deaminasehistidine-proline-rich glycoproteinzinc chaperonezinc binding site |
| spellingShingle | Maria Ranieri-Raggi Arthur J. G. Moir Antonio Raggi The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase Biomolecules AMP deaminase histidine-proline-rich glycoprotein zinc chaperone zinc binding site |
| title | The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase |
| title_full | The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase |
| title_fullStr | The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase |
| title_full_unstemmed | The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase |
| title_short | The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase |
| title_sort | role of histidine proline rich glycoprotein as zinc chaperone for skeletal muscle amp deaminase |
| topic | AMP deaminase histidine-proline-rich glycoprotein zinc chaperone zinc binding site |
| url | http://www.mdpi.com/2218-273X/4/2/474 |
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