Circular permutation of βB2‐crystallin changes the hierarchy of domain assembly

Abstract

The Py-crystallins form a superfamily of eye lens proteins comprised of multiple Greek motifs that are symmetrically organized into domains and higher assemblies. In the PB2-crystallin dimer each polypeptide folds into two similar domains that are related to monomeric y-crystallin by domain swapping. The crystal structure of the circularly permuted two-domain PB2 polypeptide shows that permutation converts intermolecular domain pairing into intramolecular pairing. However, the dimeric permuted protein is, in fact, half a native tetramer. This result shows how the sequential order of domains in multi-domain proteins can affect quaternary domain assembly.

Protein reconstitution and three‐dimensional domain swapping: Benefits and constraints of covalency

“…It may be no coincidence that both of these groups of proteins include enzymes that have been co‐opted for structural roles, and domain swapping could be relevant to this adaptation. In the case of one lens crystallin, circular permutation alters the hierarchy of domain assembly involving domain swapping, again reflecting the interdependency of levels in protein structural organization (Wright et al 1998). Other potential biological benefits of domain swapping may include the possibility to use it as a switch for inactivating proteins.…”

Laser light‐scattering evidence for an altered association of βB1‐crystallin deamidated in the connecting peptide

“…Subunits in the βγ‐crystallin family have two domain regions joined by a connecting peptide (Blundell et al 1981; Bax et al 1990). The connecting peptide has been proposed to be important in determining the domain–domain interactions (Wright et al 1998). Each tightly folded domain has two Greek key motifs comprised of four β‐pleated sheet strands (Lapatto et al 1991).…”

The evolution of monomeric and oligomeric βγ‐type crystallins

“…This was based on the following findings: a γ ‐ type protein remains monomeric when its γ ‐ type linker is replaced by a β‐type linker [46]. Likewise, a β‐type protein remains a dimer when its original linker is replaced with a γ ‐ type linker [56], as described previously [49]. In these experiments, the exchanged sequences comprised residues 82–87, as underlined in the alignment of γ ‐ and β‐type crystallins (Table 1.)…”

“…the determinants of interdomain association, intramolecular or intermolecular), are the hydrophobic interdomain patches, the interdomain linker peptides, and the terminal extensions. These have been the precise targets selected by the London and Regensburg research groups in their investigations on the structural determinants and the evolution of the b-type and c-type crystallins [7,25,[44][45][46][47][48][49][50][51].…”