A five-residue motif for the design of domain swapping in proteins.

TitleA five-residue motif for the design of domain swapping in proteins.
Publication TypeJournal Article
Year of Publication2019
AuthorsNandwani N, Surana P, Negi H, Mascarenhas NM, Udgaonkar JB, Das R, Gosavi S
JournalNat Commun
Volume10
Issue1
Pagination452
Date Published2019 Jan 28
ISSN2041-1723
KeywordsAmino 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.

DOI10.1038/s41467-019-08295-x
Alternate JournalNat Commun
PubMed ID30692525
PubMed Central IDPMC6349918
© Copyright 2016 - 2018 National Centre for Biological Sciences