Thermodynamic stability of a kappaI immunoglobulin light chain: relevance to multiple myeloma.


Immunoglobulin light chains have two similar domains, each with a hydrophobic core surrounded by beta-sheet layers, and a highly conserved disulfide bond. Differential scanning calorimetry and circular dichroism were used to study the folding and stability of MM-kappaI, an Ig LC of kappaI subtype purified from the urine of a multiple myeloma patient. The complete primary structure of MM-kappaI was determined by Edman sequence analysis and mass spectrometry. The protein was found to contain a cysteinyl post-translational modification at Cys(214). Protein stability and conformation of MM-kappaI 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-kappaI 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-kappaI was reduced and protein unfolding was irreversible at pH 4.8, thus suggesting that different pathways are utilized in thermal and chemical unfolding. Study holds ProTherm entries: 19220, 19221, 19222, 19223, 19224, 19225 Extra Details: hydrophobic core; beta-sheet; sequence analysis; pathways

Submission Details

ID: 436KKDd24

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:51 p.m.

Version: 1

Publication Details
Chung CM;Chiu JD;Connors LH;Gursky O;Lim A;Dykstra AB;Liepnieks J;Benson MD;Costello CE;Skinner M;Walsh MT,Biophys. J. (2005) Thermodynamic stability of a kappaI immunoglobulin light chain: relevance to multiple myeloma. PMID:15792972
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Immunoglobulin kappa variable 1D-33 P01594 KV133_HUMAN
100.0 Immunoglobulin kappa variable 1D-33 P01593 KVD33_HUMAN
99.0 Immunoglobulin kappa variable 4-1 P06312 KV401_HUMAN