Driving forces in amyloidosis: How does a light chain make a heavy heart?

Daniel Otzen

doi:10.1016/j.jbc.2021.100785

Driving forces in amyloidosis: How does a light chain make a heavy heart?

Interdisciplinary Nanoscience Center - INANO-MBG, iNANO-huset

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research

Abstract

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.

Original language	English
Article number	100785
Journal	The Journal of Biological Chemistry
Volume	296
Pages (from-to)	100785
ISSN	0021-9258
DOIs	https://doi.org/10.1016/j.jbc.2021.100785
Publication status	Published - 2021

Keywords

Amyloidosis/genetics
Humans
Immunoglobulin Light Chains/chemistry
Mutation
Protein Conformation

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10.1016/j.jbc.2021.100785

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title = "Driving forces in amyloidosis: How does a light chain make a heavy heart?",

abstract = "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.",

keywords = "Amyloidosis/genetics, Humans, Immunoglobulin Light Chains/chemistry, Mutation, Protein Conformation",

author = "Daniel Otzen",

year = "2021",

doi = "10.1016/j.jbc.2021.100785",

language = "English",

volume = "296",

pages = "100785",

journal = "The Journal of Biological Chemistry",

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T1 - Driving forces in amyloidosis

T2 - How does a light chain make a heavy heart?

AU - Otzen, Daniel

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 -

Driving forces in amyloidosis: How does a light chain make a heavy heart?

Abstract

Keywords

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