Effects of succinylation on thermal induced amyloid formation in Concanavalin A

Dipartimento di Scienze Fisiche e Astronomiche, Università di Palermo, Via Archirafi 36, Palermo, Italy.
European Biophysics Journal (Impact Factor: 2.22). 10/2007; 36(7):733-41. DOI: 10.1007/s00249-007-0181-z
Source: PubMed


We have recently shown that upon slight thermal destabilization the legume lectin Concanavalin A may undergo two different aggregation processes, leading, respectively, to amyloid fibrils at high pH and amorphous aggregates at low pH. Here we present an experimental study on the amyloid aggregation of Succinyl Concanavalin A, which is a dimeric active variant of Concanavalin. The results show that, as for the native protein, the fibrillation process appears to be favoured by alkaline pH, far from the isoelectric point of the protein. Moreover, it strongly depends on temperature and requires large conformational changes both at secondary and tertiary structure level. With respect to the native protein, the succinyl derivative forms amyloid fibrils in considerably longer times and with a minor exposure of hydrophobic regions. At physiological conditions, Concanavalin A still displays a sizeable tendency to form amyloid fibril, while the succinyl variant does not. A close correlation was observed between the progress of amyloid formation and a narrowing of the tryptophans fluorescence emission band, indicating a reduction of protein conformational heterogeneity in amyloid fibrils.

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    • "Also, Con A has significant structural homology to the human serum amyloid protein (SAP) that is present in in vivo amyloid deposits [22]. Moreover, the absence of disulphide bonds in its structure enhances its flexibility, favoring conformational changes at the tertiary structure level [23]. Finally, the aggregation process of Con A is also associated with its antitumor activity [24], [25] and was found to be related to its property of inducing apoptosis on tumoral cells [26], [27]. "
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    • "Finally, ordered protein aggregates can be of great interest in technological applications as a new potential nano-materials that can be exploited by research, industry and medicine [5]. As described in many studies, aggregation phenomena result from a partial unfolding of the tertiary structure of the protein and from the conformational changes of secondary structure as well [6] [7] [8]. Indeed, from recent studies on thermal aggregation process, we have concluded that the first step of aggregation consists on a partial opening of the protein native conformation. "
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