RESEARCH ARTICLE


Regions which are Responsible for Swapping are also Responsible for Folding and Misfolding



Oxana V Galzitskaya*
Institute of Protein Research, Russian Academy of Sciences, Institutskaya str. 4, Pushchino, Moscow Region, 142290, Russia


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© Oxana V. Galzitskaya; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia; Tel: +7(4967) 318275; Fax: +7(4967) 318435; E-mail: ogalzit@vega.protres.ru


Abstract

Domain swapping is a term used to describe a process when two or more protein chains exchange identical structural elements. Some cases of amyloid formation can be explained through a domain swapping mechanism therefore this deserves theoretical consideration and studying. It has been demonstrated that diverse proteins in sequence and structure are able to oligomerize via domain swapping. This allows us to suggest that the exchangeable regions are important in folding and misfolding processes of proteins, i.e. the residues from the swapping regions are typically incorporated into the native structure early during its formation. The modeling of folding of the proteins with swapped domains demonstrates that the regions exchanged in the oligomeric form in most cases are also responsible for folding and misfolding. For 11 out of 17 proteins, swapping regions intersect with the predicted amyloidogenic regions. Moreover, for 10 out of 17 proteins, high Φ-values (>0.5) belong to residues from the swapping regions. Our data confirm that the exchangeable regions are important in folding, misfolding, and domain swapping processes of the proteins, therefore the suggestion that domain swapping can serve as a mechanism for functional interconversion between monomers and oligomers is likely to be correct.

Keywords: Folding, misfolding, swapping mechanism, amyloid formation, oligomerization, folding nucleus.