Proline Residues as Switches in Conformational Changes Leading to Amyloid Fibril Formation

Abstract

Here we discuss studies of the structure, folding, oligomerization and amyloid fibril formation of several proline mutants of human stefin B, which is a protein inhibitor of lysosomal cysteine cathepsins and a member of the cystatin family. The structurally important prolines in stefin B are responsible for the slow folding phases and facilitate domain swapping (Pro 74) and loop swapping (Pro 79). Moreover, our findings are compared to β2-microglobulin, a protein involved in dialysis-related amyloidosis. The assessment of the contribution of proline residues to the process of amyloid fibril formation may shed new light on the critical molecular events involved in conformational disorders.

Comparative effects of trifluoromethyl- and methyl-group substitutions in proline

“…[1][2][3][4][5][6][7] The secondary amino group of Pro creates a tertiary amide-based backbone structure that is prone to cis-trans isomerization issues, which is sometimes responsible for the special role of Pro in protein folding. [4][5][6][7][8] Additionally, the cyclic nature of the Pro residue restricts the molecular conformation to certain envelope-type states of the pyrrolidine ring. [9][10][11][12] As the only coded amino acid with a restricted f torsion, Pro is typically positioned in specific structural contexts in biological systems relative to other amino acid residues.…”

Selenium biofortification ofPleurotusspecies and its effect on yield, phytochemical profiles, and protein chemistry of fruiting bodies

“…This amino acid can bind to the cations (and thus Se ions) or protons as it contains a single hydrogen atom attached to nitrogen atom (Morgan & Rubenstein, ). Moreover, the hydrophobicity of the proline is considered to play a vital role in disruption of the secondary structure of a protein leading to formation of novel secondary structures (Morgan & Rubenstein, ; Taler‐Vercic et al, ). Moreover, the hydrophobicity of the proline is anticipated to play a vital role in disruption of the secondary structure of a protein leading to formation of novel secondary structures (Morgan & Rubenstein, ; Taler‐Vercic et al, ).…”

“…Moreover, the hydrophobicity of the proline is considered to play a vital role in disruption of the secondary structure of a protein leading to formation of novel secondary structures (Morgan & Rubenstein, ; Taler‐Vercic et al, ). Moreover, the hydrophobicity of the proline is anticipated to play a vital role in disruption of the secondary structure of a protein leading to formation of novel secondary structures (Morgan & Rubenstein, ; Taler‐Vercic et al, ). Wu, Ding, Li, Zhang, and Wu () also showed incorporation of selenium into proteins of enriched Lentinus edodes mushroom.…”

Destabilization of β‐amyloid aggregates by thrombin derived peptide: plausible role of thrombin in neuroprotection

“…Hydrophobicity coupled with recognition patterns is suggested to be the key determinants in the interaction between β‐sheet breaker peptides and Aβ peptide . T3 displayed a more pronounced impairment of the aggregation cascade, despite the fact that Pro, a well‐known β‐sheet breaker , is a common residue between T3, T4 and T6. The hydrophobicity indices of all the peptides were calculated , and it was observed that T3 had expressed the highest hydrophobicity of 11.6 (Table ).…”

“…The hydrophobicity indices of all the peptides were calculated , and it was observed that T3 had expressed the highest hydrophobicity of 11.6 (Table ). The presence of recurrent Val in T3 possibly provides a better steric zippering as Val and Ile have a strong conformational preference, followed by Pro, which then possibly puts a constraint by inducing a possible cis/trans interconversion resulting in destabilization of the Aβ aggregate .…”