TY - JOUR

T1 - β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis

AU - Сулацкая, Анна Игоревна

AU - Косолапова, Анастасия Олеговна

AU - Бобылёв, Александр

AU - Белоусов, Михаил Владимирович

AU - Антонец, Кирилл Сергеевич

AU - Сулацкий, М.И.

AU - Кузнецова, Ирина

AU - Туроверов, Константин

AU - Степаненко, О.В.

AU - Нижников, Антон Александрович

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzer-.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Insoluble protein aggregates with fibrillar morphology called amyloids and β-barrel proteins both share a β-sheet-rich structure. Correctly folded β-barrel proteins can not only function in monomeric (dimeric) form, but also tend to interact with one another—followed, in several cases, by formation of higher order oligomers or even aggregates. In recent years, findings proving that β-barrel proteins can adopt cross-β amyloid folds have emerged. Different β-barrel proteins were shown to form amyloid fibrils in vitro. The formation of functional amyloids in vivo by β-barrel proteins for which the amyloid state is native was also discovered. In particular, several prokaryotic and eukaryotic proteins with β-barrel domains were demonstrated to form amyloids in vivo, where they participate in interspecies interactions and nutrient storage, respectively. According to recent observations, despite the variety of primary structures of amyloid-forming proteins, most of them can adopt a conformational state with the β-barrel topology. This state can be intermediate on the pathway of fibrillogenesis (“on-pathway state”), or can be formed as a result of an alternative assembly of partially unfolded monomers (“off-pathway state”). The β-barrel oligomers formed by amyloid proteins possess toxicity, and are likely to be involved in the development of amyloidoses, thus representing promising targets for potential therapy of these incurable diseases. Considering rapidly growing discoveries of the amyloid-forming β-barrels, we may suggest that their real number and diversity of functions are significantly higher than identified to date, and represent only “the tip of the iceberg”. Here, we summarize the data on the amyloid-forming β-barrel proteins, their physicochemical properties, and their biological functions, and discuss probable means and consequences of the amyloidogenesis of these proteins, along with structural relationships between these two widespread types of β-folds.

AB - Insoluble protein aggregates with fibrillar morphology called amyloids and β-barrel proteins both share a β-sheet-rich structure. Correctly folded β-barrel proteins can not only function in monomeric (dimeric) form, but also tend to interact with one another—followed, in several cases, by formation of higher order oligomers or even aggregates. In recent years, findings proving that β-barrel proteins can adopt cross-β amyloid folds have emerged. Different β-barrel proteins were shown to form amyloid fibrils in vitro. The formation of functional amyloids in vivo by β-barrel proteins for which the amyloid state is native was also discovered. In particular, several prokaryotic and eukaryotic proteins with β-barrel domains were demonstrated to form amyloids in vivo, where they participate in interspecies interactions and nutrient storage, respectively. According to recent observations, despite the variety of primary structures of amyloid-forming proteins, most of them can adopt a conformational state with the β-barrel topology. This state can be intermediate on the pathway of fibrillogenesis (“on-pathway state”), or can be formed as a result of an alternative assembly of partially unfolded monomers (“off-pathway state”). The β-barrel oligomers formed by amyloid proteins possess toxicity, and are likely to be involved in the development of amyloidoses, thus representing promising targets for potential therapy of these incurable diseases. Considering rapidly growing discoveries of the amyloid-forming β-barrels, we may suggest that their real number and diversity of functions are significantly higher than identified to date, and represent only “the tip of the iceberg”. Here, we summarize the data on the amyloid-forming β-barrel proteins, their physicochemical properties, and their biological functions, and discuss probable means and consequences of the amyloidogenesis of these proteins, along with structural relationships between these two widespread types of β-folds.

KW - Amyloid

KW - Amyloid aggregation

KW - Amyloid fibrils

KW - Amyloidosis

KW - Protein aggregation

KW - β-barrel proteins

KW - COLD-SHOCK PROTEIN

KW - FIBRIL FORMATION

KW - DNA-BINDING DOMAIN

KW - beta-barrel proteins

KW - amyloidosis

KW - CRYSTAL-STRUCTURE

KW - amyloid aggregation

KW - GREEN FLUORESCENT PROTEIN

KW - AMINO-ACID-SEQUENCE

KW - amyloid

KW - OUTER-MEMBRANE PROTEIN

KW - amyloid fibrils

KW - protein aggregation

KW - SEED STORAGE PROTEINS

KW - EXTRACELLULAR-SUPEROXIDE DISMUTASE

KW - GFP-LIKE PROTEINS

UR - http://www.scopus.com/inward/record.url?scp=85117321934&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/9a9ac205-6e4a-3468-b660-bde700f2600b/

U2 - 10.3390/ijms222111316

DO - 10.3390/ijms222111316

M3 - Review article

C2 - 34768745

VL - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 21

M1 - 11316

ER -