Immunoglobulin light chain amyloid aggregation

Luis M. Blancas-Mejia, Pinaki Misra, Christopher J. Dick, Shawna A. Cooper, Keely R. Redhage, Michael R. Bergman, Torri L. Jordan, Khansaa Maar, Marina Ramirez-Alvarado

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Light chain (AL) amyloidosis is a devastating, complex, and incurable protein misfolding disease. It is characterized by an abnormal proliferation of plasma cells (fully differentiated B cells) producing an excess of monoclonal immunoglobulin light chains that are secreted into circulation, where the light chains misfold, aggregate as amyloid fibrils in target organs, and cause organ dysfunction, organ failure, and death. In this article, we will review the factors that contribute to AL amyloidosis complexity, the findings by our laboratory from the last 16 years and the work from other laboratories on understanding the structural, kinetics, and thermodynamic contributions that drive immunoglobulin light chain-associated amyloidosis. We will discuss the role of cofactors and the mechanism of cellular damage. Last, we will review our recent findings on the high resolution structure of AL amyloid fibrils. AL amyloidosis is the best example of protein sequence diversity in misfolding diseases, as each patient has a unique combination of germline donor sequences and multiple amino acid mutations in the protein that forms the amyloid fibril.

Original languageEnglish (US)
Pages (from-to)10664-10674
Number of pages11
JournalChemical Communications
Volume54
Issue number76
DOIs
StatePublished - Jan 1 2018

Fingerprint

Immunoglobulin Light Chains
Amyloid
Agglomeration
Proteins
Cells
Thermodynamics
Plasmas
Amino acids
Amino Acids
Kinetics

ASJC Scopus subject areas

  • Catalysis
  • Electronic, Optical and Magnetic Materials
  • Ceramics and Composites
  • Chemistry(all)
  • Surfaces, Coatings and Films
  • Metals and Alloys
  • Materials Chemistry

Cite this

Blancas-Mejia, L. M., Misra, P., Dick, C. J., Cooper, S. A., Redhage, K. R., Bergman, M. R., ... Ramirez-Alvarado, M. (2018). Immunoglobulin light chain amyloid aggregation. Chemical Communications, 54(76), 10664-10674. https://doi.org/10.1039/C8CC04396E

Immunoglobulin light chain amyloid aggregation. / Blancas-Mejia, Luis M.; Misra, Pinaki; Dick, Christopher J.; Cooper, Shawna A.; Redhage, Keely R.; Bergman, Michael R.; Jordan, Torri L.; Maar, Khansaa; Ramirez-Alvarado, Marina.

In: Chemical Communications, Vol. 54, No. 76, 01.01.2018, p. 10664-10674.

Research output: Contribution to journalArticle

Blancas-Mejia, LM, Misra, P, Dick, CJ, Cooper, SA, Redhage, KR, Bergman, MR, Jordan, TL, Maar, K & Ramirez-Alvarado, M 2018, 'Immunoglobulin light chain amyloid aggregation', Chemical Communications, vol. 54, no. 76, pp. 10664-10674. https://doi.org/10.1039/C8CC04396E
Blancas-Mejia LM, Misra P, Dick CJ, Cooper SA, Redhage KR, Bergman MR et al. Immunoglobulin light chain amyloid aggregation. Chemical Communications. 2018 Jan 1;54(76):10664-10674. https://doi.org/10.1039/C8CC04396E
Blancas-Mejia, Luis M. ; Misra, Pinaki ; Dick, Christopher J. ; Cooper, Shawna A. ; Redhage, Keely R. ; Bergman, Michael R. ; Jordan, Torri L. ; Maar, Khansaa ; Ramirez-Alvarado, Marina. / Immunoglobulin light chain amyloid aggregation. In: Chemical Communications. 2018 ; Vol. 54, No. 76. pp. 10664-10674.
@article{2a64a08137244b018fef2df3228402fd,
title = "Immunoglobulin light chain amyloid aggregation",
abstract = "Light chain (AL) amyloidosis is a devastating, complex, and incurable protein misfolding disease. It is characterized by an abnormal proliferation of plasma cells (fully differentiated B cells) producing an excess of monoclonal immunoglobulin light chains that are secreted into circulation, where the light chains misfold, aggregate as amyloid fibrils in target organs, and cause organ dysfunction, organ failure, and death. In this article, we will review the factors that contribute to AL amyloidosis complexity, the findings by our laboratory from the last 16 years and the work from other laboratories on understanding the structural, kinetics, and thermodynamic contributions that drive immunoglobulin light chain-associated amyloidosis. We will discuss the role of cofactors and the mechanism of cellular damage. Last, we will review our recent findings on the high resolution structure of AL amyloid fibrils. AL amyloidosis is the best example of protein sequence diversity in misfolding diseases, as each patient has a unique combination of germline donor sequences and multiple amino acid mutations in the protein that forms the amyloid fibril.",
author = "Blancas-Mejia, {Luis M.} and Pinaki Misra and Dick, {Christopher J.} and Cooper, {Shawna A.} and Redhage, {Keely R.} and Bergman, {Michael R.} and Jordan, {Torri L.} and Khansaa Maar and Marina Ramirez-Alvarado",
year = "2018",
month = "1",
day = "1",
doi = "10.1039/C8CC04396E",
language = "English (US)",
volume = "54",
pages = "10664--10674",
journal = "Chemical Communications",
issn = "1359-7345",
publisher = "Royal Society of Chemistry",
number = "76",

}

TY - JOUR

T1 - Immunoglobulin light chain amyloid aggregation

AU - Blancas-Mejia, Luis M.

AU - Misra, Pinaki

AU - Dick, Christopher J.

AU - Cooper, Shawna A.

AU - Redhage, Keely R.

AU - Bergman, Michael R.

AU - Jordan, Torri L.

AU - Maar, Khansaa

AU - Ramirez-Alvarado, Marina

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Light chain (AL) amyloidosis is a devastating, complex, and incurable protein misfolding disease. It is characterized by an abnormal proliferation of plasma cells (fully differentiated B cells) producing an excess of monoclonal immunoglobulin light chains that are secreted into circulation, where the light chains misfold, aggregate as amyloid fibrils in target organs, and cause organ dysfunction, organ failure, and death. In this article, we will review the factors that contribute to AL amyloidosis complexity, the findings by our laboratory from the last 16 years and the work from other laboratories on understanding the structural, kinetics, and thermodynamic contributions that drive immunoglobulin light chain-associated amyloidosis. We will discuss the role of cofactors and the mechanism of cellular damage. Last, we will review our recent findings on the high resolution structure of AL amyloid fibrils. AL amyloidosis is the best example of protein sequence diversity in misfolding diseases, as each patient has a unique combination of germline donor sequences and multiple amino acid mutations in the protein that forms the amyloid fibril.

AB - Light chain (AL) amyloidosis is a devastating, complex, and incurable protein misfolding disease. It is characterized by an abnormal proliferation of plasma cells (fully differentiated B cells) producing an excess of monoclonal immunoglobulin light chains that are secreted into circulation, where the light chains misfold, aggregate as amyloid fibrils in target organs, and cause organ dysfunction, organ failure, and death. In this article, we will review the factors that contribute to AL amyloidosis complexity, the findings by our laboratory from the last 16 years and the work from other laboratories on understanding the structural, kinetics, and thermodynamic contributions that drive immunoglobulin light chain-associated amyloidosis. We will discuss the role of cofactors and the mechanism of cellular damage. Last, we will review our recent findings on the high resolution structure of AL amyloid fibrils. AL amyloidosis is the best example of protein sequence diversity in misfolding diseases, as each patient has a unique combination of germline donor sequences and multiple amino acid mutations in the protein that forms the amyloid fibril.

UR - http://www.scopus.com/inward/record.url?scp=85053734177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053734177&partnerID=8YFLogxK

U2 - 10.1039/C8CC04396E

DO - 10.1039/C8CC04396E

M3 - Article

C2 - 30087961

AN - SCOPUS:85053734177

VL - 54

SP - 10664

EP - 10674

JO - Chemical Communications

JF - Chemical Communications

SN - 1359-7345

IS - 76

ER -