TY - JOUR
T1 - Driving forces in amyloidosis
T2 - How does a light chain make a heavy heart?
AU - Otzen, Daniel
N1 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2021
Y1 - 2021
N2 - Light chain amyloidosis (AL) is a fatal disorder wherein immunoglobulin light chain misfolds and aggregates, leading to amyloid plaques in various organs. Patient-specific mutations in the antibody VL domain are tightly linked to amyloidosis, but how these mutations drive AL is unknown. In recent work, Rottenaicher et al. analyze five mutations found in the variable (VL) domain of a cardiac AL patient. Their data suggest that decreased VL stability and increased flexibility in the core of VL, caused by mutations outside of this core, could be key to aggregation, and highlight the delicate balancing act required for antibody maturation to enable antigen recognition while not altering protein biophysics.
AB - Light chain amyloidosis (AL) is a fatal disorder wherein immunoglobulin light chain misfolds and aggregates, leading to amyloid plaques in various organs. Patient-specific mutations in the antibody VL domain are tightly linked to amyloidosis, but how these mutations drive AL is unknown. In recent work, Rottenaicher et al. analyze five mutations found in the variable (VL) domain of a cardiac AL patient. Their data suggest that decreased VL stability and increased flexibility in the core of VL, caused by mutations outside of this core, could be key to aggregation, and highlight the delicate balancing act required for antibody maturation to enable antigen recognition while not altering protein biophysics.
KW - Amyloidosis/genetics
KW - Humans
KW - Immunoglobulin Light Chains/chemistry
KW - Mutation
KW - Protein Conformation
U2 - 10.1016/j.jbc.2021.100785
DO - 10.1016/j.jbc.2021.100785
M3 - Journal article
C2 - 34019874
SN - 0021-9258
VL - 296
SP - 100785
JO - The Journal of Biological Chemistry
JF - The Journal of Biological Chemistry
M1 - 100785
ER -