4im6
From Proteopedia
LRR domain from human NLRP1
Structural highlights
Disease[NALP1_HUMAN] Genetic variations in NLRP1 are associated with susceptibility to vitiligo (VTLG) [MIM:193200]. VTLG is a pigmentary disorder of the skin characterized by circumscribed depigmented macules and patches, commonly on extensor aspects of extremities, on the face or neck and in skin folds. It is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. It is a multifactorial disorder with a complex etiology probably including autoimmune mechanisms, and is associated with an elevated risk of other autoimmune diseases.[1] Genetic variations in NLRP1 gene are associated with susceptibility to vitiligo-associated multiple autoimmune disease type 1 (VAMAS1) [MIM:606579]. VAMAS1 is an autoimmune disorder characterized by the association of vitiligo with several autoimmune and autoinflammatory diseases including autoimmune thyroid disease, rheumatoid arthritis and systemic lupus erythematosus.[2] Function[NALP1_HUMAN] Able to form cytoplasmic structures termed death effector filaments. Enhances APAF1 and cytochrome c-dependent activation of pro-caspase-9 and consecutive apoptosis. Stimulates apoptosis through activation of caspase-3. Involved in activation of caspase-1 and caspase-5 as part of the NALP1 inflammasome complex which leads to processing and release of IL1B and IL18. Binds ATP.[3] [4] [5] Publication Abstract from PubMedThe NOD-like receptor NLRP1 (NLR family, pyrin domain containing 1) senses the presence of the bacterial cell wall component l-muramyl dipeptide (MDP) inside the cell. We determined the crystal structure of the LRR domain of human NLRP1 in the absence of MDP to a resolution of 1.65A. The fold of the structure can be assigned to the ribonuclease inhibitor-like class of LRR proteins. We compared our structure with X-ray models of the LRR domains of NLRX1 and NLRC4 and a homology model of the LRR domain of NOD2. We conclude that the MDP binding site of NLRP1 is not located in the LRR domain. Crystal structure of the leucine-rich repeat domain of the NOD-like receptor NLRP1: implications for binding of muramyl dipeptide.,Reubold TF, Hahne G, Wohlgemuth S, Eschenburg S FEBS Lett. 2014 Sep 17;588(18):3327-32. doi: 10.1016/j.febslet.2014.07.017. Epub , 2014 Jul 24. PMID:25064844[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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