ß-Strand-mediated Domain-swapping in the Absence of Hydrophobic Core Repacking.
J Mol Biol
; 436(2): 168405, 2024 01 15.
Article
em En
| MEDLINE
| ID: mdl-38104859
ABSTRACT
Domain swapping is a process wherein a portion of a protein is exchanged with its counterpart in another copy of the molecule, resulting in the formation of homo-oligomers with concomitant repacking of a hydrophobic core. Here, we report domain swapping triggered upon modifying a ß-hairpin sequence within a single-layer ß-sheet (SLB) of a model protein, OspA that did not involve the formation of a reorganized hydrophobic core. The replacement of two ß-hairpin sequences with a Gly-Gly and shorteing of a ß-hairpin resulted in a protein that formed two distinct crystal structures under similar conditions one was monomeric, similar to the parental molecule, whereas the other was a domain-swapped dimer, mediated by an intermolecular ß-sheet in the SLB portion. Based on the dimer interface structure, we replaced the Gly-Gly sequence with three-residue sequences that enable the formation of a consecutive intermolecular ß-sheet, including the Cys-Thr-Cys sequence that formed a stable disulfide-linked dimer. These results provide new insights into protein folding, evolution, and the designability of protein structure.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dobramento de Proteína
/
Conformação Proteica em Folha beta
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article