Lepidosaur ß-keratin chains with four 34-residue repeats: Modelling reveals a potential filament-crosslinking role

•The four 34-residue repeat chains may have repeats in different filaments thereby crosslinking them together.•This would endow the epidermal appendage with lateral integrity and structural reinforcement.•This is the first suggestion of a potential crosslinker in lepidosaur ß-keratin filaments. ß-ke...

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Published inJournal of structural biology Vol. 209; no. 1; p. 107413
Main Authors Fraser, R.D. Bruce, Parry, David A.D.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.01.2020
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Summary:•The four 34-residue repeat chains may have repeats in different filaments thereby crosslinking them together.•This would endow the epidermal appendage with lateral integrity and structural reinforcement.•This is the first suggestion of a potential crosslinker in lepidosaur ß-keratin filaments. ß-keratin chains contain a characteristic and homologous 34-residue sequence, which is believed to adopt a twisted ß-sheet conformation that assembles in an antiparallel manner with a similar sheet in a second chain to form a ß-sandwich. These sandwiches are, in turn, related to one another by a left-handed four-fold screw axis to generate a helical structure that forms the core of the 3.4 nm diameter filaments observed by electron microscopy and deduced from X-ray fibre diffraction. Recently, it has been shown that one ß-keratin chain, with a molecular weight approximately twice that of the majority of ß-keratin chains, is conserved across the lepidosaurs (lizards, snakes and tuatara). Uniquely, it contains four 34-residue repeats. Although this chain is a minor component the observation that the entire chain shows a high degree of sequence conservation between species suggests an important structural/functional role in vivo. Modelling shows that only six families of structures are physically possible. In three of these the repeats exist within a single filament and might therefore act in a filament nucleation role. In the second three families the repeats exist in two, three or four filaments, implying that their function may be to act as an inter-filament crosslinker, thereby providing lateral reinforcement to the epidermal appendage. The favoured model is one in which the first two repeats form a β-sandwich in one filament and the second two repeats form a β-sandwich in a neighbouring filament. Links between alternating up- and down-pointing β-sheets would provide optimum connectivity.
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ISSN:1047-8477
1095-8657
DOI:10.1016/j.jsb.2019.107413