Evolutionary and functional relationships between the basic and acidic β-crystallins

Slingsby, C., Driessen, H.P.C., Mahadevan, D., Bax, Benjamin ORCID: https://orcid.org/0000-0003-1940-3785 and Blundell, T.L. 1988. Evolutionary and functional relationships between the basic and acidic β-crystallins. Experimental Eye Research 46 (3) , pp. 375-403. 10.1016/S0014-4835(88)80027-7

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Abstract

β-Crystallins are complex oligomers composed of many related subunits. In order to understand their interactions we have built molecular models of several bovine β-crystallins, based on their sequence similarity to the well-defined γ-II crystallin structure, using interactive computer graphics techniques. Their common origin with γ-crystallin is displayed in both the retention of four-fold sequence repeats of critical residues involved with stabilizing a folded β-hairpin and the conservation of core-filling hydrophobic side-chains. The β-crystallins have been built as bilobal molecules with each domain composed of two ‘Greek key motifs which associate about an approximate two-fold axis to form β-sheets. The β-crystallin sequences have previously been shown to comprise two families, the basic and acidic subunits, which have extensions of sequence. The three-dimensional models show how the two families appear to stabilize the folded β-hairpin in the N- and C-terminal domains in ways which suggest that they have diverged from a common ancestor in different ways. Acidic β-crystallins, like γ-crystallins, have a regular array of charges on their N-terminal domain which has been interrupted in basic β-crystallins by hydrophobic residues which may be related to the presence of a C-terminal extension. β-Crystallins are more highly charged than γ-crystallins although their charge density is higher in certain regions of the N-terminal domain, particularly in βB1-crystallin. β-crystallins also differ from γ-crystallins in the virtual absence of core-filling sulphydryl groups whereas they have numerous sulphurcontaining side-chains together with tryptophan and histidine rings protruding from the globular domains, particularly in the acidic subunits. The burial of these residues in subunit contacts is consistent with their spectroscopic and electrostatic properties. Protein subunit aggregation commonly occurs through hydrophobic interaction or β-sheet extension. Analysis of the subunit surfaces has identified an N-terminal hydrophobic region common to βB1 and βB2 whereas a C-terminal hydrophobic loop region is common to βB1 and βA1 and may be correlated with their association properties. It is suggested that the polar C-terminal domain of βB2 contributes towards the solubility of higher aggregates by interactions involving β-sheet structure.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier
ISSN:	0014-4835
Last Modified:	23 Oct 2022 14:03
URI:	https://orca.cardiff.ac.uk/id/eprint/112657

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