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Structural studies of the C-terminal 19-peptide of serum amyloid A and its Pro → Ala variants interacting with human cystatin C.
- Source :
-
Journal of molecular recognition : JMR [J Mol Recognit] 2015 Jul; Vol. 28 (7), pp. 413-26. Date of Electronic Publication: 2015 Mar 02. - Publication Year :
- 2015
-
Abstract
- Serum amyloid A (SAA) is a multifunctional acute-phase protein whose concentration in serum increases markedly following a number of chronic inflammatory and neoplastic diseases. Prolonged high SAA level may give rise to reactive systemic amyloid A (AA) amyloidosis, where the N-terminal segment of SAA is deposited as amyloid fibrils. Besides, recently, well-documented association of SAA with high-density lipoprotein or glycosaminoglycans, in particular heparin/heparin sulfate (HS), and specific interaction between SAA and human cystatin C (hCC), the ubiquitous inhibitor of cysteine proteases, was proved. Using a combination of selective proteolytic excision and high-resolution mass spectrometry, a hCC binding site in the SAA sequence was determined as SAA(86-104). The role of this SAA C-terminal fragment as a ligand-binding locus is still not clear. It was postulated important in native SAA folding and in pathogenesis of AA amyloidosis. In the search of conformational details of this SAA fragment, we did its structure and affinity studies, including its selected double/triple Pro → Ala variants. Our results clearly show that the SAA(86-104) 19-peptide has rather unordered structure with bends in its C-terminal part, which is consistent with the previous results relating to the whole protein. The results of affinity chromatography, fluorescent ELISA-like test, CD and NMR studies point to an importance of proline residues on structure of SAA(86-104). Conformational details of SAA fragment, responsible for hCC binding, may help to understand the objective of hCC-SAA complex formation and its importance for pathogenesis of reactive amyloid A amyloidosis.<br /> (Copyright © 2015 John Wiley & Sons, Ltd.)
- Subjects :
- Alanine chemistry
Calorimetry, Differential Scanning
Chromatography, Affinity
Circular Dichroism
Cystatin C metabolism
Humans
Peptides metabolism
Proline chemistry
Protein Conformation
Protein Isoforms chemistry
Protein Isoforms metabolism
Protein Structure, Tertiary
Serum Amyloid A Protein metabolism
Cystatin C chemistry
Peptides chemistry
Serum Amyloid A Protein chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1099-1352
- Volume :
- 28
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of molecular recognition : JMR
- Publication Type :
- Academic Journal
- Accession number :
- 25736604
- Full Text :
- https://doi.org/10.1002/jmr.2457