A scalable strategy to solve structures of PDZ domains and their complexes.

Fiche publication

Date publication

avril 2022

Journal

Acta crystallographica. Section D, Structural biology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr TRAVE Gilles , Dr GOGL Gergo

Tous les auteurs :
Cousido-Siah A, Carneiro L, Kostmann C, Ecsedi P, Nyitray L, Trave G, Gogl G

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/35362473

Résumé

The human PDZome represents one of the largest globular domain families in the human proteome, with 266 instances. These globular domains typically interact with C-terminal peptide motifs found in thousands of human proteins. Despite previous efforts, not all PDZ domains have experimentally solved structures and most of their complexes remain to be solved. Here, a simple and cost-effective strategy is proposed for the crystallization of PDZ domains and their complexes. A human annexin A2 fusion tag was used as a crystallization chaperone and the structures of nine PDZ domains were solved, including five domains that had not yet been solved. Finally, these novel experimental structures were compared with AlphaFold predictions and it is speculated how predictions and experimental methods could cooperate in order to investigate the structural landscapes of entire domain families and interactomes.