The BRICHOS Domain, Amyloid Fibril Formation, and Their Relationship

• Published in: Biochemistry (Easton) 2013-10, Vol.52 (43), p.7523-7531
• Main Authors: Knight, Stefan D, Presto, Jenny, Linse, Sara, Johansson, Jan
• Format: Article
• Language: English
• Subjects: Amyloid - chemistry; Amyloid - drug effects; Amyloid - metabolism; Amyloidosis - drug therapy; Amyloidosis - metabolism; Animals; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Biologi; Biological Sciences; Conserved Sequence; Dementia - drug therapy; Dementia - metabolism; Humans; Medicin och hälsovetenskap; Medicinsk bioteknologi; Medicinsk bioteknologi (inriktn. mot cellbiologi (inkl. stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci); Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - therapeutic use; Models, Molecular; Natural Sciences; Naturvetenskap; Nootropic Agents - chemistry; Nootropic Agents - metabolism; Nootropic Agents - therapeutic use; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - metabolism; Peptide Fragments - therapeutic use; Protein Interaction Domains and Motifs; Protein Precursors - chemistry; Protein Precursors - metabolism; Pulmonary Surfactant-Associated Protein C - chemistry; Pulmonary Surfactant-Associated Protein C - genetics; Pulmonary Surfactant-Associated Protein C - metabolism; Pulmonary Surfactant-Associated Protein C - therapeutic use; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Recombinant Proteins - therapeutic use; Sequence Homology, Amino Acid
• ISSN: 0006-2960; 1520-4995; 1520-4995
• DOI: 10.1021/bi400908x

Amyloid diseases are defined by tissue deposition of insoluble, fibrillar β-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 β-sheet structures, including amyloid β-peptide associated with Alzheimer’s 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 β-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 β-prone regions.