Amyloid Fibril Formation from Sequences of a Natural β-Structured Fibrous Protein, the Adenovirus Fiber

Abstract

Amyloid fibrils are fibrous ␤-structures that derive from abnormal folding and assembly of peptides and proteins. Despite a wealth of structural studies on amyloids, the nature of the amyloid structure remains elusive; possible connections to natural, ␤-structured fibrous motifs have been suggested. In this work we focus on understanding amyloid structure and formation from sequences of a natural, ␤-structured fibrous protein. We show that short peptides (25 to 6 amino acids) corresponding to repetitive sequences from the adenovirus fiber shaft have an intrinsic capacity to form amyloid fibrils as judged by electron microscopy, Congo Red binding, infrared spectroscopy, and x-ray fiber diffraction. In the presence of the globular C-terminal domain of the protein that acts as a trimerization motif, the shaft sequences adopt a triple-stranded, ␤-fibrous motif. We discuss the possible structure and arrangement of these sequences within the amyloid fibril, as compared with the one adopted within the native structure. A 6-amino acid peptide, corresponding to the last ␤-strand of the shaft, was found to be sufficient to form amyloid fibrils. Structural analysis of these amyloid fibrils suggests that perpendicular stacking of ␤-strand repeat units is an underlying common feature of amyloid formation.

Crystal structure of an intramolecular chaperone mediating triple–β-helix folding

“…The rigid elongated shape allows triple β-helix-comprising proteins to protrude from a pathogen's surface in order to interact with flexible host cell receptors, like lipopolysaccharides 9 . However, proper assembly of triple-β-helical folds poses to be difficult in the absence of a trimerization domain 10 . Hence, most triple β-helices depend on a C-terminal extension for trimerization and correct assembly 11 .…”

Disorders of Protein Conformation as a Typical Component of Various Human Disease Pathogenesis

“…Так, при изу-чении фибриллярного белка аденовируса показано, что один конец его фиксирован на капсиде, другой связыва-ется с клеткой, а в промежуточной последовательности присутствуют бета-участки. Пептиды (начиная уже с шести аминокислот в них), первичная структура кото-рых соответствует части таковой участков бета-цепей указанного нормального белка, оказались достаточными для формирования в растворах амилоидных фибрилл [7]. Важно также то, что конформеры патогенных прионов (формы прионных белков, различающиеся по конфор-мационной структуре между собой) в процессе эволюции могут подвергаться отбору с образованием менее стабиль-ного и, следовательно, максимально быстро реплициру-ющегося типа [8].…”

New sources and instrumentation for neutrons in biology

“…This type of diffraction predominates in diffraction studies of many filamentous viruses, drug-DNA and protein-DNA complexes and is also a key aspect of changes in ordering that occur during structural transitions [67]. Major opportunities exist to exploit selective deuteration so that particular parts of a structure can be highlighted [68], as well as for the investigation of key problems in the study of amyloid fibres [69].…”

“…a multi-subunit protein system), selective deuteration allows effective modelling of individual components [17,19,20,23,77,78]. Similar approaches are equally powerful when studying biological membranes with NR [69]. At higher resolution, perdeuteration of macromolecular systems in crystals and fibres provides a major advantage through the enhanced coherent scattering power of substituted deuterium and the elimination of hydrogen incoherent scattering.…”