Thermodynamic stability of a κI immunoglobulin light chain

Relevance to multiple myeloma

Connie M. Chung, Jenny D. Chiu, Lawreen H. Connors, Olga Gursky, Amareth Lim, Andrew B. Dykstra, Juris Liepnieks, Merrill Benson, Catherine E. Costello, Martha Skinner, Mary T. Walsh

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Immunoglobulin light chains have two similar domains, each with a hydrophobia core surrounded by β-sheet layers, and a highly conserved disulfide bond. Differential scanning calorimetry and circular dichroism were used to study the folding and stability of MM-κI, an Ig LC of κI subtype purified from the urine of a multiple myeloma patient. The complete primary structure of MM-κI was determined by Edman sequence analysis and mass spectrometry. The protein was found to contain a cysteinyl post-translational modification at Cys214. Protein stability and conformation of MM-κI as a function of temperature or denaturant conditions at pH 7.4 and 4.8 were investigated. At pH 4.8, calorimetry demonstrated that MM-κI undergoes an incomplete, cooperative, partially reversible thermal unfolding with increased unfolding temperature and calorimetric enthalpy as compared to pH 7.4. Secondary and tertiary structural analyses provided evidence to support the presence of unfolding intermediates. Chemical denaturation resulted in more extensive protein unfolding. The stability of MM-κI was reduced and protein unfolding was irreversible at pH 4.8, thus suggesting that different pathways are utilized in thermal and chemical unfolding.

Original languageEnglish
Pages (from-to)4232-4242
Number of pages11
JournalBiophysical Journal
Volume88
Issue number6
DOIs
StatePublished - Jun 2005

Fingerprint

Immunoglobulin Light Chains
Multiple Myeloma
Thermodynamics
Protein Unfolding
Hot Temperature
Protein Conformation
Calorimetry
Temperature
Rabies
Protein Stability
Differential Scanning Calorimetry
Post Translational Protein Processing
Circular Dichroism
Disulfides
Sequence Analysis
Mass Spectrometry
Urine
Proteins

ASJC Scopus subject areas

  • Biophysics

Cite this

Chung, C. M., Chiu, J. D., Connors, L. H., Gursky, O., Lim, A., Dykstra, A. B., ... Walsh, M. T. (2005). Thermodynamic stability of a κI immunoglobulin light chain: Relevance to multiple myeloma. Biophysical Journal, 88(6), 4232-4242. https://doi.org/10.1529/biophysj.105.061317

Thermodynamic stability of a κI immunoglobulin light chain : Relevance to multiple myeloma. / Chung, Connie M.; Chiu, Jenny D.; Connors, Lawreen H.; Gursky, Olga; Lim, Amareth; Dykstra, Andrew B.; Liepnieks, Juris; Benson, Merrill; Costello, Catherine E.; Skinner, Martha; Walsh, Mary T.

In: Biophysical Journal, Vol. 88, No. 6, 06.2005, p. 4232-4242.

Research output: Contribution to journalArticle

Chung, CM, Chiu, JD, Connors, LH, Gursky, O, Lim, A, Dykstra, AB, Liepnieks, J, Benson, M, Costello, CE, Skinner, M & Walsh, MT 2005, 'Thermodynamic stability of a κI immunoglobulin light chain: Relevance to multiple myeloma', Biophysical Journal, vol. 88, no. 6, pp. 4232-4242. https://doi.org/10.1529/biophysj.105.061317
Chung, Connie M. ; Chiu, Jenny D. ; Connors, Lawreen H. ; Gursky, Olga ; Lim, Amareth ; Dykstra, Andrew B. ; Liepnieks, Juris ; Benson, Merrill ; Costello, Catherine E. ; Skinner, Martha ; Walsh, Mary T. / Thermodynamic stability of a κI immunoglobulin light chain : Relevance to multiple myeloma. In: Biophysical Journal. 2005 ; Vol. 88, No. 6. pp. 4232-4242.
@article{da3919acd86b48c98fd31e9a60383a00,
title = "Thermodynamic stability of a κI immunoglobulin light chain: Relevance to multiple myeloma",
abstract = "Immunoglobulin light chains have two similar domains, each with a hydrophobia core surrounded by β-sheet layers, and a highly conserved disulfide bond. Differential scanning calorimetry and circular dichroism were used to study the folding and stability of MM-κI, an Ig LC of κI subtype purified from the urine of a multiple myeloma patient. The complete primary structure of MM-κI was determined by Edman sequence analysis and mass spectrometry. The protein was found to contain a cysteinyl post-translational modification at Cys214. Protein stability and conformation of MM-κI as a function of temperature or denaturant conditions at pH 7.4 and 4.8 were investigated. At pH 4.8, calorimetry demonstrated that MM-κI undergoes an incomplete, cooperative, partially reversible thermal unfolding with increased unfolding temperature and calorimetric enthalpy as compared to pH 7.4. Secondary and tertiary structural analyses provided evidence to support the presence of unfolding intermediates. Chemical denaturation resulted in more extensive protein unfolding. The stability of MM-κI was reduced and protein unfolding was irreversible at pH 4.8, thus suggesting that different pathways are utilized in thermal and chemical unfolding.",
author = "Chung, {Connie M.} and Chiu, {Jenny D.} and Connors, {Lawreen H.} and Olga Gursky and Amareth Lim and Dykstra, {Andrew B.} and Juris Liepnieks and Merrill Benson and Costello, {Catherine E.} and Martha Skinner and Walsh, {Mary T.}",
year = "2005",
month = "6",
doi = "10.1529/biophysj.105.061317",
language = "English",
volume = "88",
pages = "4232--4242",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "6",

}

TY - JOUR

T1 - Thermodynamic stability of a κI immunoglobulin light chain

T2 - Relevance to multiple myeloma

AU - Chung, Connie M.

AU - Chiu, Jenny D.

AU - Connors, Lawreen H.

AU - Gursky, Olga

AU - Lim, Amareth

AU - Dykstra, Andrew B.

AU - Liepnieks, Juris

AU - Benson, Merrill

AU - Costello, Catherine E.

AU - Skinner, Martha

AU - Walsh, Mary T.

PY - 2005/6

Y1 - 2005/6

N2 - Immunoglobulin light chains have two similar domains, each with a hydrophobia core surrounded by β-sheet layers, and a highly conserved disulfide bond. Differential scanning calorimetry and circular dichroism were used to study the folding and stability of MM-κI, an Ig LC of κI subtype purified from the urine of a multiple myeloma patient. The complete primary structure of MM-κI was determined by Edman sequence analysis and mass spectrometry. The protein was found to contain a cysteinyl post-translational modification at Cys214. Protein stability and conformation of MM-κI as a function of temperature or denaturant conditions at pH 7.4 and 4.8 were investigated. At pH 4.8, calorimetry demonstrated that MM-κI undergoes an incomplete, cooperative, partially reversible thermal unfolding with increased unfolding temperature and calorimetric enthalpy as compared to pH 7.4. Secondary and tertiary structural analyses provided evidence to support the presence of unfolding intermediates. Chemical denaturation resulted in more extensive protein unfolding. The stability of MM-κI was reduced and protein unfolding was irreversible at pH 4.8, thus suggesting that different pathways are utilized in thermal and chemical unfolding.

AB - Immunoglobulin light chains have two similar domains, each with a hydrophobia core surrounded by β-sheet layers, and a highly conserved disulfide bond. Differential scanning calorimetry and circular dichroism were used to study the folding and stability of MM-κI, an Ig LC of κI subtype purified from the urine of a multiple myeloma patient. The complete primary structure of MM-κI was determined by Edman sequence analysis and mass spectrometry. The protein was found to contain a cysteinyl post-translational modification at Cys214. Protein stability and conformation of MM-κI as a function of temperature or denaturant conditions at pH 7.4 and 4.8 were investigated. At pH 4.8, calorimetry demonstrated that MM-κI undergoes an incomplete, cooperative, partially reversible thermal unfolding with increased unfolding temperature and calorimetric enthalpy as compared to pH 7.4. Secondary and tertiary structural analyses provided evidence to support the presence of unfolding intermediates. Chemical denaturation resulted in more extensive protein unfolding. The stability of MM-κI was reduced and protein unfolding was irreversible at pH 4.8, thus suggesting that different pathways are utilized in thermal and chemical unfolding.

UR - http://www.scopus.com/inward/record.url?scp=22244451652&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22244451652&partnerID=8YFLogxK

U2 - 10.1529/biophysj.105.061317

DO - 10.1529/biophysj.105.061317

M3 - Article

VL - 88

SP - 4232

EP - 4242

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 6

ER -