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Title: Inhibition of amyloid fiber assembly by both BiP and its target peptide.

Abstract

Immunoglobulin light chain (LC) normally is a soluble, secreted protein, but some LC assemble into ordered fibrils whose deposition in tissues results in amyloidosis and organ failure. Here we reconstitute fibril formation in vitro and show that preformed fibrils can nucleate polymerization of soluble LC. This prion-like behavior has important physiological implications, since somatic mutations generate multiple related LC sequences. Furthermore, we demonstrate that fibril formation in vitro and aggregation of whole LC within cells are inhibited by BiP and by a synthetic peptide that is identical to a major LC binding site for BiP. We propose that LC form fibrils via an interprotein loop swap and that the underlying conformational change should be amenable to drug therapy.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH)
OSTI Identifier:
949246
Report Number(s):
ANL/BIO/JA-39060
TRN: US201012%%46
DOE Contract Number:  
DE-AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
Immunity
Additional Journal Information:
Journal Volume: 13; Journal Issue: 4 ; Oct. 2000
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; CHAINS; CONFORMATIONAL CHANGES; DEPOSITION; FIBERS; IMMUNOGLOBULINS; IN VITRO; ORGANS; PEPTIDES; POLYMERIZATION; SOMATIC MUTATIONS; TARGETS; THERAPY

Citation Formats

Davis, D P, Raffen, R, Vogen, S, Williamson, E, Stevens, F J, Argon, Y, Biosciences Division, and Univ. of Chicago. Inhibition of amyloid fiber assembly by both BiP and its target peptide.. United States: N. p., 2000. Web. doi:10.1016/S1074-7613(00)00043-1.
Davis, D P, Raffen, R, Vogen, S, Williamson, E, Stevens, F J, Argon, Y, Biosciences Division, & Univ. of Chicago. Inhibition of amyloid fiber assembly by both BiP and its target peptide.. United States. https://doi.org/10.1016/S1074-7613(00)00043-1
Davis, D P, Raffen, R, Vogen, S, Williamson, E, Stevens, F J, Argon, Y, Biosciences Division, and Univ. of Chicago. 2000. "Inhibition of amyloid fiber assembly by both BiP and its target peptide.". United States. https://doi.org/10.1016/S1074-7613(00)00043-1.
@article{osti_949246,
title = {Inhibition of amyloid fiber assembly by both BiP and its target peptide.},
author = {Davis, D P and Raffen, R and Vogen, S and Williamson, E and Stevens, F J and Argon, Y and Biosciences Division and Univ. of Chicago},
abstractNote = {Immunoglobulin light chain (LC) normally is a soluble, secreted protein, but some LC assemble into ordered fibrils whose deposition in tissues results in amyloidosis and organ failure. Here we reconstitute fibril formation in vitro and show that preformed fibrils can nucleate polymerization of soluble LC. This prion-like behavior has important physiological implications, since somatic mutations generate multiple related LC sequences. Furthermore, we demonstrate that fibril formation in vitro and aggregation of whole LC within cells are inhibited by BiP and by a synthetic peptide that is identical to a major LC binding site for BiP. We propose that LC form fibrils via an interprotein loop swap and that the underlying conformational change should be amenable to drug therapy.},
doi = {10.1016/S1074-7613(00)00043-1},
url = {https://www.osti.gov/biblio/949246}, journal = {Immunity},
number = 4 ; Oct. 2000,
volume = 13,
place = {United States},
year = {Sun Oct 01 00:00:00 EDT 2000},
month = {Sun Oct 01 00:00:00 EDT 2000}
}