Thermodynamic and fibril formation studies of full length immunoglobulin light chain AL-09 and its germline protein using scan rate dependent thermal unfolding

Luis M. Blancas-Mejía, Timothy J. Horn, Marta Marin-Argany, Matthew T Auton, Alexander Tischer, Marina Ramirez-Alvarado

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Abstract Light chain (AL) amyloidosis is a fatal disease where monoclonal immunoglobulin light chains deposit as insoluble amyloid fibrils. For many years it has been considered that AL amyloid deposits are formed primarily by the variable domain, while its constant domain has been considered not to be amyloidogenic. However recent studies identify full length (FL) light chains as part of the amyloid deposits. In this report, we compare the stabilities and amyloidogenic properties of two light chains, an amyloid-associated protein AL-09 FL, and its germline protein κ I O18/O8 FL (IGKV 1-33). We demonstrate that the thermal unfolding for both proteins is irreversible and scan rate dependent, with similar stability parameters compared to their V<inf>L</inf> counterparts. In addition, the constant domain seems to modulate their amyloidogenic properties and affect the morphology of the amyloid fibrils. These results allow us to understand the role of the kappa constant domain in AL amyloidosis.

Original languageEnglish (US)
Article number5846
Pages (from-to)13-20
Number of pages8
JournalBiophysical Chemistry
Volume207
DOIs
StatePublished - Aug 12 2015

Fingerprint

Immunoglobulin Light Chains
Thermodynamics
Amyloid
Hot Temperature
Light
Amyloid Plaques
Amyloidosis
Proteins
Deposits
Amyloidogenic Proteins
Protein Unfolding

Keywords

  • Amyloid fibril formation
  • Irreversible thermal unfolding
  • Kinetic stability
  • Light chain amyloidosis
  • Protein aggregation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Organic Chemistry

Cite this

Thermodynamic and fibril formation studies of full length immunoglobulin light chain AL-09 and its germline protein using scan rate dependent thermal unfolding. / Blancas-Mejía, Luis M.; Horn, Timothy J.; Marin-Argany, Marta; Auton, Matthew T; Tischer, Alexander; Ramirez-Alvarado, Marina.

In: Biophysical Chemistry, Vol. 207, 5846, 12.08.2015, p. 13-20.

Research output: Contribution to journalArticle

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AU - Auton, Matthew T

AU - Tischer, Alexander

AU - Ramirez-Alvarado, Marina

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AB - Abstract Light chain (AL) amyloidosis is a fatal disease where monoclonal immunoglobulin light chains deposit as insoluble amyloid fibrils. For many years it has been considered that AL amyloid deposits are formed primarily by the variable domain, while its constant domain has been considered not to be amyloidogenic. However recent studies identify full length (FL) light chains as part of the amyloid deposits. In this report, we compare the stabilities and amyloidogenic properties of two light chains, an amyloid-associated protein AL-09 FL, and its germline protein κ I O18/O8 FL (IGKV 1-33). We demonstrate that the thermal unfolding for both proteins is irreversible and scan rate dependent, with similar stability parameters compared to their VL counterparts. In addition, the constant domain seems to modulate their amyloidogenic properties and affect the morphology of the amyloid fibrils. These results allow us to understand the role of the kappa constant domain in AL amyloidosis.

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