Protein Dynamics group uses state of art experimental and computational methods to elucidate the relations between protein conformation and function
Talin variant P229S compromises integrin activation
We studied a de novo heterozygous c.685C>T (p.Pro229Ser) variant in the TLN1 gene from a patient with a complex phenotype. The mutation, identified by Prof. Joseph Church (Children’s Hospital Los Angeles), is located in the talin head region at the interface between the F2 and F3 domains. Our lab studied the characteristics of the mutated talin in talin-knockout cells and using computational modelling, and Prof. Ben Goult lab (University of Kent) examined the influence of the mutation on biochemical characteristics of talin head. We found that p.P229S talin variant influences adhesion dynamics that result from disturbance of the F2-F3 domain interface in the talin head. This causes defects in integrin activation, adhesion and cell migration.
Talin variant P229S compromises integrin activation and associates with multifaceted clinical symptoms
Latifeh Azizi, Lorena Varela, Paula Turkk, Vasyl V Mykuliak, Sanna Korpela, Teemu O Ihalainen, Joseph Church, Vesa P Hytönen, Benjamin T Goult
Human Molecular Genetics 2022, ddac163