The BRICHOS Domain, Amyloid Fibril Formation, and Their Relationship

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• 作者：Stefan D. Knight ; Jenny Presto ; Sara Linse ; Jan Johansson
• 刊名：Biochemistry
• 出版年：2013
• 出版时间：October 29, 2013
• 年：2013
• 卷：52
• 期：43
• 页码：7523-7531
• 全文大小：443K
• 年卷期：v.52,no.43(October 29, 2013)
• ISSN：1520-4995

文摘

Amyloid diseases are defined by tissue deposition of insoluble, fibrillar 尾-sheet polymers of specific proteins, but it appears that toxic oligomeric species rather than the fibrils are the main cause of tissue degeneration. Many proteins can form amyloid-like fibrils in vitro, but only 30 proteins have been found to cause mammalian amyloid disease, suggesting that physiological mechanisms that protect against amyloid formation exist. The transmembrane region of lung surfactant protein C precursor (proSP-C) forms amyloid-like fibrils in vitro, and SP-C amyloid has been found in lung tissue from patients with interstitial lung disease (ILD). ProSP-C contains a BRICHOS domain, in which many ILD-associated mutations are localized, and the BRICHOS domain can prevent SP-C from forming amyloid-like fibrils. Recent data suggest that recombinant BRICHOS domains from proSP-C and Bri2 (associated with familial dementia and amyloid formation) interact with peptides with a strong propensity to form 尾-sheet structures, including amyloid 尾-peptide associated with Alzheimer鈥檚 disease. Such interactions efficiently delay formation of fibrils and oligomers. The BRICHOS domain is defined at the sequence level and is found in 10 distantly related proprotein families. These have widely different or unknown functions, but several of the proteins are associated with human disease. Structural modeling of various BRICHOS domains, based on the X-ray structure of the proSP-C BRICHOS domain, identifies a conserved region that is structurally complementary to the 尾-sheet- and/or amyloid-prone regions in the BRICHOS domain-containing proproteins. These observations make the BRICHOS domain the first example of a chaperone-like domain with specificity for 尾-prone regions.