1t77
From Proteopedia
Crystal structure of the PH-BEACH domains of human LRBA/BGL
Structural highlights
Disease[LRBA_HUMAN] Defects in LRBA are the cause of immunodeficiency, common variable, type 8, with autoimmunity (CVID8) [MIM:614700]. An autosomal recessive immunologic disorder associated with defective B-cell differentiation and decreased or absent antibody production. Affected individuals have early-childhood onset of recurrent infections, particularly respiratory infections, and also develop variable autoimmune disorders, including idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and inflammatory bowel disease.[1] Function[LRBA_HUMAN] May be involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe beige and Chediak-Higashi syndrome (BEACH) domain defines a large family of eukaryotic proteins that have diverse cellular functions in vesicle trafficking, membrane dynamics, and receptor signaling. The domain is the only module that is highly conserved among all of these proteins, but the exact functions of this domain and the molecular basis for its actions are currently unknown. Our previous studies showed that the BEACH domain is preceded by a novel, weakly conserved pleckstrin homology (PH) domain. We report here the crystal structure at 2.4 A resolution of the PH-BEACH domain of human LRBA/BGL. The PH domain has the same backbone fold as canonical PH domains, despite sharing no sequence homology with them. However, our binding assays demonstrate that the PH domain in the BEACH proteins cannot bind phospholipids. The BEACH domain contains a core of several partially extended peptide segments that is flanked by helices on both sides. The structure suggests intimate association between the PH and the BEACH domains, and surface plasmon resonance studies confirm that the two domains of the protein FAN have high affinity for each other, with a K(d) of 120 nM. Crystal structure of the PH-BEACH domains of human LRBA/BGL.,Gebauer D, Li J, Jogl G, Shen Y, Myszka DG, Tong L Biochemistry. 2004 Nov 30;43(47):14873-80. PMID:15554694[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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