A model for amyloid fibril formation in immunoglobulin light chains based on comparison of amyloidogenic and benign proteins and specific antibody binding

Ritu Khurana, Pierre O. Souillac, Alisa C. Coats, Lauren Minert, Cristian Ionescu-Zanetti, Sue A. Carter, Alan Solomon, Anthony L. Fink

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In an attempt to understand the mechanism of amyloid fibril formation in light chain amyloidosis, the properties of amyloidogenic (SMA) and benign (LEN) immunoglobulin light chain variable domains (VL) were compared. The conformations of LEN and SMA were measured using secondary and tertiary structural probes over the pH range from 2 and 8. At all pH values, LEN was more stable than SMA. The CD spectra of LEN at pH 2 were comparable to those of SMA at pH 7.5, indicating that the low pH conformation of LEN closely resembles that of SMA at physiological pH. At low pH, a relatively unfolded intermediate conformation is populated for SMA and rapidly leads to amyloid fibrils. The lack of such an intermediate with LEN, is attributed to sequence differences and accounts for the lack of LEN fibrils in the absence of agitation. A κIV-specific monoclonal antibody that recognizes the N-terminal of SMA caused unraveling of the fibrils to the protofilaments and was observed to bind to one end of SMA protofilaments by atomic force microscopy. The antibody result indicates that each protofilament is asymmetric with different ends. A model for the formation of fibrils by SMA is proposed.

Original languageEnglish (US)
Pages (from-to)97-109
Number of pages13
JournalAmyloid
Volume10
Issue number2
DOIs
StatePublished - Jan 1 2003

Fingerprint

Immunoglobulin Light Chains
Amyloidogenic Proteins
Amyloid
Antibodies
Atomic Force Microscopy
Amyloidosis
Monoclonal Antibodies
Light

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Khurana, R., Souillac, P. O., Coats, A. C., Minert, L., Ionescu-Zanetti, C., Carter, S. A., ... Fink, A. L. (2003). A model for amyloid fibril formation in immunoglobulin light chains based on comparison of amyloidogenic and benign proteins and specific antibody binding. Amyloid, 10(2), 97-109. https://doi.org/10.3109/13506120309041731

A model for amyloid fibril formation in immunoglobulin light chains based on comparison of amyloidogenic and benign proteins and specific antibody binding. / Khurana, Ritu; Souillac, Pierre O.; Coats, Alisa C.; Minert, Lauren; Ionescu-Zanetti, Cristian; Carter, Sue A.; Solomon, Alan; Fink, Anthony L.

In: Amyloid, Vol. 10, No. 2, 01.01.2003, p. 97-109.

Research output: Contribution to journalArticle

Khurana, Ritu ; Souillac, Pierre O. ; Coats, Alisa C. ; Minert, Lauren ; Ionescu-Zanetti, Cristian ; Carter, Sue A. ; Solomon, Alan ; Fink, Anthony L. / A model for amyloid fibril formation in immunoglobulin light chains based on comparison of amyloidogenic and benign proteins and specific antibody binding. In: Amyloid. 2003 ; Vol. 10, No. 2. pp. 97-109.
@article{68fe6b705ea945fdb0cb998143527f21,
title = "A model for amyloid fibril formation in immunoglobulin light chains based on comparison of amyloidogenic and benign proteins and specific antibody binding",
abstract = "In an attempt to understand the mechanism of amyloid fibril formation in light chain amyloidosis, the properties of amyloidogenic (SMA) and benign (LEN) immunoglobulin light chain variable domains (VL) were compared. The conformations of LEN and SMA were measured using secondary and tertiary structural probes over the pH range from 2 and 8. At all pH values, LEN was more stable than SMA. The CD spectra of LEN at pH 2 were comparable to those of SMA at pH 7.5, indicating that the low pH conformation of LEN closely resembles that of SMA at physiological pH. At low pH, a relatively unfolded intermediate conformation is populated for SMA and rapidly leads to amyloid fibrils. The lack of such an intermediate with LEN, is attributed to sequence differences and accounts for the lack of LEN fibrils in the absence of agitation. A κIV-specific monoclonal antibody that recognizes the N-terminal of SMA caused unraveling of the fibrils to the protofilaments and was observed to bind to one end of SMA protofilaments by atomic force microscopy. The antibody result indicates that each protofilament is asymmetric with different ends. A model for the formation of fibrils by SMA is proposed.",
author = "Ritu Khurana and Souillac, {Pierre O.} and Coats, {Alisa C.} and Lauren Minert and Cristian Ionescu-Zanetti and Carter, {Sue A.} and Alan Solomon and Fink, {Anthony L.}",
year = "2003",
month = "1",
day = "1",
doi = "10.3109/13506120309041731",
language = "English (US)",
volume = "10",
pages = "97--109",
journal = "Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis",
issn = "1350-6129",
publisher = "Informa Healthcare",
number = "2",

}

TY - JOUR

T1 - A model for amyloid fibril formation in immunoglobulin light chains based on comparison of amyloidogenic and benign proteins and specific antibody binding

AU - Khurana, Ritu

AU - Souillac, Pierre O.

AU - Coats, Alisa C.

AU - Minert, Lauren

AU - Ionescu-Zanetti, Cristian

AU - Carter, Sue A.

AU - Solomon, Alan

AU - Fink, Anthony L.

PY - 2003/1/1

Y1 - 2003/1/1

N2 - In an attempt to understand the mechanism of amyloid fibril formation in light chain amyloidosis, the properties of amyloidogenic (SMA) and benign (LEN) immunoglobulin light chain variable domains (VL) were compared. The conformations of LEN and SMA were measured using secondary and tertiary structural probes over the pH range from 2 and 8. At all pH values, LEN was more stable than SMA. The CD spectra of LEN at pH 2 were comparable to those of SMA at pH 7.5, indicating that the low pH conformation of LEN closely resembles that of SMA at physiological pH. At low pH, a relatively unfolded intermediate conformation is populated for SMA and rapidly leads to amyloid fibrils. The lack of such an intermediate with LEN, is attributed to sequence differences and accounts for the lack of LEN fibrils in the absence of agitation. A κIV-specific monoclonal antibody that recognizes the N-terminal of SMA caused unraveling of the fibrils to the protofilaments and was observed to bind to one end of SMA protofilaments by atomic force microscopy. The antibody result indicates that each protofilament is asymmetric with different ends. A model for the formation of fibrils by SMA is proposed.

AB - In an attempt to understand the mechanism of amyloid fibril formation in light chain amyloidosis, the properties of amyloidogenic (SMA) and benign (LEN) immunoglobulin light chain variable domains (VL) were compared. The conformations of LEN and SMA were measured using secondary and tertiary structural probes over the pH range from 2 and 8. At all pH values, LEN was more stable than SMA. The CD spectra of LEN at pH 2 were comparable to those of SMA at pH 7.5, indicating that the low pH conformation of LEN closely resembles that of SMA at physiological pH. At low pH, a relatively unfolded intermediate conformation is populated for SMA and rapidly leads to amyloid fibrils. The lack of such an intermediate with LEN, is attributed to sequence differences and accounts for the lack of LEN fibrils in the absence of agitation. A κIV-specific monoclonal antibody that recognizes the N-terminal of SMA caused unraveling of the fibrils to the protofilaments and was observed to bind to one end of SMA protofilaments by atomic force microscopy. The antibody result indicates that each protofilament is asymmetric with different ends. A model for the formation of fibrils by SMA is proposed.

UR - http://www.scopus.com/inward/record.url?scp=0043204678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0043204678&partnerID=8YFLogxK

U2 - 10.3109/13506120309041731

DO - 10.3109/13506120309041731

M3 - Article

VL - 10

SP - 97

EP - 109

JO - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis

JF - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis

SN - 1350-6129

IS - 2

ER -