Turk J Immunol. 2024; 12(1): 37-46 | DOI: 10.4274/tji.galenos.2023.21939

Structure and Function of the LRBA Protein

Ege Ezen¹, Mehmet Cihangir Çatak², Feyza Bayram Çatak³, Sofia Piepoli¹, Pegah Zahedimaram¹, Ecem Ultanýr¹, Safa Barýþ⁴, Batu Erman^1
1Boðaziçi University Faculty of Arts and Sciences, Department of Molecular Biology and Genetics, Ýstanbul, Turkey
²Marmara University Faculty of Medicine, Department of Pediatric Allergy and Immunology, Ýstanbul, Turkey
³Marmara University, Ýstanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Ýstanbul, Turkey
⁴Marmara University, The Iþýl Berat Barlan Center for Translational Medicine, Ýstanbul, Turkey
⁵University of California Faculty of Medicine, Department of Microbiology and Environmental Toxicology, Santa Cruz, USA

Beige and Chediak (BEACH) domain-containing protein (BDCP) family proteins are large cytoplasmic adaptor proteins associated with endosomal and lysosomal recycling and degradation pathways. These proteins have C-terminal PH, Beach and WD40 domains, whose structures are solved or can be predicted using recently developed algorithms such as Alphafold. Family members such as LRBA, LYST and NBEAL2 are implicated in human disease. LRBA was shown to be responsible for the re-shuttling of the T-cell co-inhibitory receptor CTLA4 back to the plasma membrane after internalization and lack or mutation of LRBA results in surface deficiency of CTLA4 in regulatory and activated T lymphocytes. The large molecular size of these proteins indicates that they may have pleiotropic functions in the immune system and beyond. Sequence and domain structure similarities between the proteins suggest that a level of redundancy may be present, which could potentially result in new therapeutic avenues.

Keywords: LRBA, LYST, CTLA4, immune dysregulation, common variable immunodeficiency, Chédiak Higashi syndrome

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