The effect of nucleotide changes on the three-dimensional structure of immune receptor complexes

Francesca Capon (primary)
Medical and Molecular Genetics
King's College London
Franca Fraternali (secondary)
Randall centre for cell and molecular biophysics
King's College London


Characterising the consequences of naturally occurring nucleotide changes is a powerful approach to the identification of amino acid residues that are critical to protein function. While, numerous computational tools have been developed to predict variant effects in-silico, these have variable accuracy and rarely take into account protein three-dimensional structures.

Here we propose to combine experimental and computational methods to identify the amino acid substitutions that are more likely to de-stabilize the structure of multi-protein complexes. As the discrimination between benign and deleterious changes can be especially challenging for immune genes, the project will focus on variants that affect inflammatory proteins.


Catapano M, Vergnano M, Romano M, Mahil SK, Choon SE, Burden AD, Young HS, Carr IM, Lachmann HJ, Lombardi G, Smith CH, Ciccarelli FD, Barker JN, Capon F. Interleukin-36 promotes systemic Type-I IFN responses in severe forms of psoriasis. J Invest Dermatol, 2020 140:816-826

Mahil SK, Catapano M, Di Meglio P, Dand N, Ahlfors H, Carr IM, Smith CH, Trembath RC, Peakman M, Wright J, Ciccarelli F, Barker JN, Capon F. An analysis of IL-36 signature genes and individuals with IL1RL2 knockout mutations validates IL-36 as a psoriasis therapeutic target. Science Translational Medicine, 2017 9:eaan2514

Laddach A, Ng JCF, Fraternali F. Pathogenic missense protein variants affect different functional pathways and proteomic features than healthy population variants. PLoS Biology 2021 19(4):e3001207

Molecules, cells and industrial biotechnology
Area of Biology
GeneticsStructural Biology
Techniques & Approaches
BiophysicsGeneticsMathematics / Statistics