03 July 2013

Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling

Researchers from Novo Nordisk Foundation Center for Protein Research in collaboration with Clinical researchers at the Centre for Chronic immunodeficiency (Freiburg, Germany) identify a hotspot for mutations in patients suffering from the devastating familial immunodeficiency XLP2. In a study published in EMBO Molecular Medicine, Mads Gyrd-Hansen and co-workers find that the region in the XIAP gene encoding the BIR2 domain is frequently mutated in XLP2 patients. Molecularly, they demonstrate that the patient-derived mutations prevent binding between XIAP and a protein (RIPK2) that links XIAP to the bacterial sensors NOD1 and NOD2, leading to impaired innate immune signalling. The findings indicate that impaired NOD1/2-dependent signalling is a unifying immune defect in XLP2 patients, suggesting that this may contribute to aspects of the disease.

Title: Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling

Authors: Rune Busk Damgaard, Berthe Katrine Fiil, Carsten Speckmann, Monica Yabal, Udo zur Stadt, Simon Bekker-Jensen, Philipp J. Jost, Stephan Ehl, Niels Mailand, Mads Gyrd-Hansen.

Link: http://onlinelibrary.wiley.com/doi/10.1002/emmm.201303090/abstract