7nuf | pdb_00007nuf

Vaccinia virus protein 018 in complex with STAT1

spinqualitylabelsall models 7nuf, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7nuf is a 2 chain structure with sequence from Homo sapiens and Vaccinia virus WR. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.0004015Å Ligands: ACE, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease STAT1_HUMAN Defects in STAT1 are the cause of STAT1 deficiency complete (STAT1D) [MIM:613796. STAT1D is a disorder characterized by susceptibility to severe mycobacterial and viral infections. Affected individuals can develop disseminated infections and die of viral illness. Defects in STAT1 are a cause of Mendelian susceptibility to mycobacterial disease (MSMD) [MIM:209950; also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. Defects in STAT1 are the cause of familial candidiasis type 7 (CANDF7) [MIM:614162. A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans. Note=STAT1 mutations in patients with autosomal dominant candidiasis lead to defective responses of type 1 and type 17 helper T-cells, characterized by reduced production of interferon-alpha, interleukin-17, and interleukin-22. These cytokines are crucial for the antifungal defense of skin and mucosa (PubMed:21714643). Function STAT1_HUMAN Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and growth factors. Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated. It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state. Becomes activated in response to KITLG/SCF and KIT signaling. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4.

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