title: Structure-function effects in primary immunodeficiencies.
abstract: Several immunodeficiency-related genes have been identified and a large number of mutations in these genes. Currently, a genetic defect has been determined in more than 2000 patients. Only recently has it become possible to address structure-function effects of these mutations in the corresponding proteins. The consequences of mutations in structure are discussed for Btk in X-linked agammaglobulinemia (XLA), Jak3 in T-B+ severe combined immunodeficiency (SCID), p47phox and p67phox in autosomal chronic granulomatous disease (CGD) and SH2D1 A in X-linked lymphoproliferatine disease (XLP). The experimental and homology modelling derived structures were used to analyze mechanisms related to these diseases.
authors.affiliation: Institute of Medical Technology, FIN-33014 University of Tampere; Tampere University Hospital, FIN-33520 Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Korpi
authors.forename: J
authors.initials: J
authors.lastname: Väliaho
authors.forename: M
authors.initials: M
authors.lastname: Vihinen
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D016208:Databases, Factual; D006105:Granulomatous Disease, Chronic / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D053616:Janus Kinase 3; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D009154:Mutation; D009252:NADPH Dehydrogenase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D010750:Phosphoproteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013329:Structure-Activity Relationship; D018909:src Homology Domains / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C085072:neutrophil cytosol factor 40K; C079789:neutrophil cytosol factor 67K; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C507933:JAK3 protein, human; D053616:Janus Kinase 3