Zinc binding agonist effect on the recognition of the β-amyloid (4–10) epitope by anti-β-amyloid antibodies

Zirah, Séverine; Ştefănescu, Raluca; Manea, Marilena; Tian, Xiaodan; Cecal, Roxana; Kozin, Sergey A.; Debey, Pascale; Rebuffat, Sylvie; Przybylski, Michael

doi:10.1016/j.bbrc.2004.06.150

Cited by 22 publications

(21 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, other results obtained by structural studies, have shown that this peptide has two metal binding sites with higher and lower affinity: copper in high affinity site is coordinated in a planar configuration with three histidines and terminus or Tyr10 and this binding site is able to bind also a zinc ion [21,22,25]. The four aminoacids proposed for zinc binding site are Tyr10, Glu11, Arg5 or the N-terminus [6,[26][27][28][29]. It has been made hypothesis about the presence for both metals in the second low affinity binding site but it is still studying [30][31][32].…”

Section: Introductionmentioning

confidence: 71%

“…It is a protein extremely sensitive to thermal denaturation [57] and has a mild antioxidant nature due to the free thiol group [58]. In fact, it is already reported that, when heated, globular proteins tend to aggregate, thanks to the contribution of intermolecular disulfide bonds [7,25,27,28] and hydrophobic interactions [47]. In particular, when the temperature increases, monomerization and partial unfolding of the protein are induced with consequent exposure of SH group and formation of an intermolecular bond with a free cysteine of a close molecule.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

See 1 more Smart Citation

Thermal aggregation of β-lactoglobulin in presence of metal ions

Navarra

Leone

Militello

2007

Biophysical Chemistry

View full text Add to dashboard Cite

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractIn this work, we report a study on the effects of zinc and copper ions on the heat-induced aggregation of β−Lactoglobulin (BLG). Kinetics investigations on aggregates growth by light scattering measurements and on secondary structure changes by FT-IR absorption measurementsshow the different role played by two metals during the whole process. In particular, the presence of zinc in solution promotes the formation of aggregates of BLG at a lower temperature than the copper. Then, fixed the temperature, formation of a large amount of aggregates, with a large dimension, is observed for the Zn-BLG in shorter time; on the contrary, the presence of the copper in solution does not affect the aggregation process but the secondary structure changes and the formation of different stronger intermolecular H-bonds, which probably lead to build a network of bonds that takes towards gelation. Our studies show as time evolution of aggregation process of BLG is dramatically affected by the presence of metal ions in solution and structural protein modifications are induced by different divalent metal ions.

show abstract

Section: Introductionmentioning

confidence: 71%

Section: Accepted M Manuscriptmentioning

confidence: 99%

Thermal aggregation of β-lactoglobulin in presence of metal ions

Navarra

Leone

Militello

2007

Biophysical Chemistry

View full text Add to dashboard Cite

show abstract

“…Studies suggested that H6, H13, and H14 at the N-terminal domain of Aβ coordinate with Zn 2þ (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Solution NMR of Zn 2þ -Aβ [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] showed that Zn 2þ is bound to these three histidines and E11 (18). A recent NMR study of Zn 2þ -Aβ proposed that Zn 2þ binds to H6, E11, H14, and D1 of rat Aβ 1-28 and to H6, E11, H13, H14, and D1 of human Aβ 1-28 (22).…”

mentioning

confidence: 99%

Zinc ions promote Alzheimer Aβ aggregation via population shift of polymorphic states

Miller

Ma²,

Nussinov³

2010

Proc. Natl. Acad. Sci. U.S.A.

286

288

View full text Add to dashboard Cite

Although a key factor in Alzheimer's disease etiology is enrichment of Zn 2þ in aggregates, and there are data suggesting that zinc promotes aggregation, how Zn 2þ -Aβ coordination promotes aggregation is elusive. Here we probe the structures and mechanisms through which Zn 2þ can affect amyloidosis. By covalently linking fragments (that have experiment-based coordinates) we observed that, in oligomeric Zn 2þ -Aβ 42 , Zn 2þ can simultaneously coordinate intra-and intermolecularly, bridging two peptides. Zinc coordination significantly decreases the solvation energy for large Zn 2þ -Aβ 42 oligomers and thus enhances their aggregation tendency. Zn 2þ binding does not change the β-sheet association around the C-terminal hydrophobic region; however, it shifts the relative population of the preexisting amyloid polymorphic ensembles. As a result, although a parallel β-sheet arrangement is still preferred, antiparallel and other less structured assemblies are stabilized, also becoming major species. Overall, Zn 2þ coordination promotes Aβ 42 aggregation leading to less uniform structures. Our replica exchange molecular dynamics simulations further reproduced an experimental observation that the increasing Zn 2þ concentration could slow down the aggregation rate, even though the aggregation rates are still much higher than in Zn 2þ -free solution.conformational selection | energy landscape | metal ions | modeling amyloid assemblies | seed polymorphism A lzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia in millions of people worldwide (1). This disease accounts for the majority of clinical senile dementia associated with the formation of senile plaques (2, 3). The primary constituent of the plaques is the aggregated Aβ 40 ∕Aβ 42 peptides in the brain; therefore, factors that influence the aggregation are of high interest.In vivo studies reported that Zn 2þ , Cu þ2 , and Fe þ3 are markedly enriched in Aβ plaques (4, 5), suggesting that these ions may act as seeding factors. Oligomerization of the Aβ peptides can be rapidly induced in the presence of Zn 2þ ions under physiological conditions (4, 6, 7). Noy et al. (8) have followed Zn 2þ ionenhanced Aβ aggregation. Studies suggested that H6, H13, and H14 at the N-terminal domain of Aβ coordinate with Zn 2þ (9-26). Solution NMR of Zn 2þ -Aβ 1-16 showed that Zn 2þ is bound to these three histidines and E11 (18). A recent NMR study of Zn 2þ -Aβ 1-28 proposed that Zn 2þ binds to H6, E11, H14, and D1 of rat Aβ 1-28 and to H6, E11, H13, H14, and D1 of human Aβ 1-28 (22). In addition, X-ray absorption spectroscopy revealed that Zn 2þ coordinates with four histidines, H13 and H14 of two adjacent monomers (23). Experimental structural data for Aβ 40 ∕Aβ 42 oligomers complexed with Zn 2þ are unavailable.Although it is believed that reducing zinc-induced Aβ aggregation can decrease toxicity (27), it was also postulated that zinc can lower Aβ toxicity by selectively precipitating aggregation intermediates (28). Key questions on the...

show abstract

“…In this structure two conformationally different regions have been observed, namely, residues 18‐42 form a β‐strand‐turn‐β‐strand motif constituting the Aβ inner intermolecular core whereas residues 1‐17 are disordered and located outside of the core thus forming a site that is not necessarily involved in amyloid stabilization and is quite accessible for interactions with partners other than Aβ. Indeed, the N‐terminal region 1‐16 was identified as the Zn/Cu‐binding domain of Aβ 12–16. Recently, the solution structure of a synthetic peptide corresponding to Aβ‐(1‐16) in Zn‐free and Zn‐bound state was resolved 17.…”

mentioning

confidence: 99%

The N‐domain of angiotensin‐converting enzyme specifically hydrolyzes the Arg‐5‐His‐6 bond of Alzheimer's Aβ‐(1‐16) peptide and its isoAsp‐7 analogue with different efficiency as evidenced by quantitative matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry

Toropygin

Kugaevskaya

Mirgorodskaya

et al. 2007

Rapid Comm Mass Spectrometry

Self Cite

View full text Add to dashboard Cite

Chronic imbalance between production and degradation of the human amyloid-beta peptide (Abeta) is assumed to play an important role in pathogenesis of Alzheimer's disease (AD). Post-translational modifications of Abeta could influence its interactions with specifically cleaving proteases and, therefore, perturb the Abeta homeostasis. The angiotensin-converting enzyme (ACE) was previously shown to degrade non-modified Abeta in vitro and in cells. In the presented work, we investigated the effect of isomerization of Asp-7, a common non-enzymatic age-related modification found in AD-associated Abeta species, on hydrolysis of Abeta by ACE. Two synthetic peptides corresponding to the Abeta region 1-16 with either Asp or isoAsp residues in position 7 were examined as monomeric soluble substrates for the N- as well as for the C-domain of ACE. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) coupled with the (18)O-labeled internal standard approach has allowed us to show that (i) the N-domain of ACE (N-ACE), but not the C-domain, selectively cleaves the Arg-5-His-6 bond in both peptides, and that (ii) N-ACE hydrolyzes the isoAsp-7 analogue more efficiently than the non-modified one. Our results demonstrate a new endopeptidase activity of N-ACE as well as high preference of the domain to recognize and hydrolyze the isomerized Abeta species that were earlier suggested to promote AD pathogenesis. The results suggest the need for further analysis of biological effects of isomerized Abeta and its interaction with ACE in AD pathogenesis.

show abstract

Zinc binding agonist effect on the recognition of the β-amyloid (4–10) epitope by anti-β-amyloid antibodies

Cited by 22 publications

References 32 publications

Thermal aggregation of β-lactoglobulin in presence of metal ions

Thermal aggregation of β-lactoglobulin in presence of metal ions

Zinc ions promote Alzheimer Aβ aggregation via population shift of polymorphic states

Contact Info

Product

Resources

About