Kinetic stability and sequence/structure studies of urine-derived Bence-Jones proteins from multiple myeloma and light chain amyloidosis patients

Luis M. Blancas-Mejía, Emily B. Martin, Angela Williams, Jonathan S. Wall, Marina Ramirez-Alvarado

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

It is now accepted that the ability of a protein to form amyloid fibrils could be associated both kinetic and thermodynamic protein folding parameters. A recent study from our laboratory using recombinant full-length (encompassing the variable and constant domain) immunoglobulin light chains found a strong kinetic control of the protein unfolding for these proteins. In this study, we are extending our analysis by using urine-derived Bence Jones proteins (BJPs) from five patients with light chain (AL) amyloidosis and four patients with multiple myeloma (MM).We observed lower stability in κ proteins compared to λ proteins (for both MM and AL proteins) in agreement with previous studies. The kinetic component of protein stability is not a universal feature of BJPs and the hysteresis observed during refolding reactions could be attributed to the inability of the protein to refold all domains.The most stable proteins exhibited 3-state unfolding transitions. While these proteins do not refold reversibly, partial refolding shows 2-state partial refolding transitions, suggesting that one of the domains (possibly the variable domain) does not refold completely. Sequences were aligned with their respective germlines and the location and nature of the mutations were analyzed. The location of the mutations were analyzed and compared with the stability and amyloidogenic properties for the proteins in this study, increasing our understanding of light chain unfolding and amyloidogenic potential.

Original languageEnglish (US)
JournalBiophysical Chemistry
DOIs
StateAccepted/In press - 2017

Fingerprint

Bence Jones Protein
Amyloidosis
Multiple Myeloma
Urine
Light
Kinetics
Protein Stability
Proteins
Protein Refolding
Immunoglobulin Light Chains
Amyloidogenic Proteins
Myeloma Proteins
Protein Unfolding
Mutation
Protein Folding
Thermodynamics
Amyloid
Protein folding
Hysteresis

Keywords

  • Bence-Jones
  • Circular dichroism
  • Kinetic stability
  • Light chain amyloidosis
  • Protein aggregation
  • Thermal unfolding

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Organic Chemistry

Cite this

Kinetic stability and sequence/structure studies of urine-derived Bence-Jones proteins from multiple myeloma and light chain amyloidosis patients. / Blancas-Mejía, Luis M.; Martin, Emily B.; Williams, Angela; Wall, Jonathan S.; Ramirez-Alvarado, Marina.

In: Biophysical Chemistry, 2017.

Research output: Contribution to journalArticle

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