Title | A five-residue motif for the design of domain swapping in proteins. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Nandwani N, Surana P, Negi H, Mascarenhas NM, Udgaonkar JB, Das R, Gosavi S |
Journal | Nat Commun |
Volume | 10 |
Issue | 1 |
Pagination | 452 |
Date Published | 2019 Jan 28 |
ISSN | 2041-1723 |
Keywords | Amino Acid Motifs, Amino Acid Sequence, Cystatin B, Hydrophobic and Hydrophilic Interactions, Models, Molecular, Mutation, Protein Engineering, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Sequence Homology, Amino Acid |
Abstract | Domain swapping is the process by which identical monomeric proteins exchange structural elements to generate dimers/oligomers. Although engineered domain swapping is a compelling strategy for protein assembly, its application has been limited due to the lack of simple and reliable design approaches. Here, we demonstrate that the hydrophobic five-residue 'cystatin motif' (QVVAG) from the domain-swapping protein Stefin B, when engineered into a solvent-exposed, tight surface loop between two β-strands prevents the loop from folding back upon itself, and drives domain swapping in non-domain-swapping proteins. High-resolution structural studies demonstrate that engineering the QVVAG stretch independently into various surface loops of four structurally distinct non-domain-swapping proteins enabled the design of different modes of domain swapping in these proteins, including single, double and open-ended domain swapping. These results suggest that the introduction of the QVVAG motif can be used as a mutational approach for engineering domain swapping in diverse β-hairpin proteins. |
DOI | 10.1038/s41467-019-08295-x |
Alternate Journal | Nat Commun |
PubMed ID | 30692525 |
PubMed Central ID | PMC6349918 |