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Infinite Assembly of Folded Proteins in Evolution, Disease, and Engineering.

ABSTRACT: Mutations and changes in a protein's environment are well known for their potential to induce misfolding and aggregation, including amyloid formation. Alternatively, such perturbations can trigger new interactions that lead to the polymerization of folded proteins. In contrast to aggregation, this process does not require misfolding and, to highlight this difference, we refer to it as agglomeration. This term encompasses the amorphous assembly of folded proteins as well as the polymerization in one, two, or three dimensions. We stress the remarkable potential of symmetric homo-oligomers to agglomerate even by single surface point mutations, and we review the double-edged nature of this potential: how aberrant assemblies resulting from agglomeration can lead to disease, but also how agglomeration can serve in cellular adaptation and be exploited for the rational design of novel biomaterials.

SUBMITTER: Garcia-Seisdedos H

PROVIDER: S-EPMC6471489 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Infinite Assembly of Folded Proteins in Evolution, Disease, and Engineering.

Garcia-Seisdedos Hector H Villegas José A JA Levy Emmanuel D ED

Angewandte Chemie (International ed. in English) 20190220 17

Mutations and changes in a protein's environment are well known for their potential to induce misfolding and aggregation, including amyloid formation. Alternatively, such perturbations can trigger new interactions that lead to the polymerization of folded proteins. In contrast to aggregation, this process does not require misfolding and, to highlight this difference, we refer to it as agglomeration. This term encompasses the amorphous assembly of folded proteins as well as the polymerization in ...[more]

PMID: 30133878

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