TY - JOUR
T1 - Comparison of amyloid fibril formation by two closely related immunoglobulin light chain variable domains
AU - Martin, Douglas J.
AU - Ramirez-Alvarado, Marina
N1 - Funding Information:
We would like to acknowledge Dr. Roshini Abraham for the contribution of patient cDNA and members of the Ramirez-Alvarado laboratory for helpful comments on the manuscript. Funding provided by NIH GM071514 (MRA), F30DK082169 (DJM), and the generous support of patients with light chain amyloidosis and the Mayo foundation.
PY - 2010/9
Y1 - 2010/9
N2 - Light chain amyloidosis AL amyloidosis is a haematological disorder in which a clonal population of B cells expands and secretes enormous amounts of the immunoglobulin light chain protein. These light chains misfold and aggregate into amyloid fibrils, leading to organ dysfunction and death. We have studied the in vitro fibril formation kinetics of two patient-derived immunoglobulin light chain variable domain proteins, designated AL-09 and AL-103, in response to changes in solution conditions. Both proteins are members of the κI O18:O8 germline and therefore are highly similar in sequence, but they presented with different clinical phenotypes. We find that AL-09 forms fibrils more readily and more rapidly than AL-103 in vitro, mirroring the clinical phenotypes of the patients and suggesting a possible connection between the fibril kinetics of the disease protein and the disease progression.
AB - Light chain amyloidosis AL amyloidosis is a haematological disorder in which a clonal population of B cells expands and secretes enormous amounts of the immunoglobulin light chain protein. These light chains misfold and aggregate into amyloid fibrils, leading to organ dysfunction and death. We have studied the in vitro fibril formation kinetics of two patient-derived immunoglobulin light chain variable domain proteins, designated AL-09 and AL-103, in response to changes in solution conditions. Both proteins are members of the κI O18:O8 germline and therefore are highly similar in sequence, but they presented with different clinical phenotypes. We find that AL-09 forms fibrils more readily and more rapidly than AL-103 in vitro, mirroring the clinical phenotypes of the patients and suggesting a possible connection between the fibril kinetics of the disease protein and the disease progression.
KW - Amyloid
KW - amyloid fibril kinetics
KW - electrostatics
KW - immunoglobulin light chain
KW - light chain amyloidosis
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U2 - 10.3109/13506129.2010.530081
DO - 10.3109/13506129.2010.530081
M3 - Article
C2 - 21077798
AN - SCOPUS:78649280232
SN - 1350-6129
VL - 17
SP - 129
EP - 136
JO - Amyloid
JF - Amyloid
IS - 3-4
ER -