Decrease in stability of human albumin with increase in protein concentration.


Abstract

The stability (reflected in denaturation temperature, Td) of defatted human albumin monomer, monitored by differential scanning calorimetry, decreases with increasing protein concentration. This is shown to be compatible with a simple model in which reversible polymerization of denatured monomer promotes unfolding. This model also predicts an increase in transition cooperativity with decreasing protein concentration whereas experimentally cooperativity decreases because the rate of thermally induced polymerization of unfolded monomer is slow relative to the scan rate of the calorimeter. The denaturation of undefatted human albumin monomer, subsaturated with high affinity endogenous long-chain fatty acid (LCFA), was previously observed by differential scanning calorimetry to be a biphasic process. Td for the first endotherm, associated with the denaturation of LCFA-poor species, decreases with increasing protein concentration similar to that for defatted monomer whereas Td for the second endotherm, associated with denaturation of LCFA-rich species, is independent of concentration. The magnitude of the concentration dependence of Td relates directly to the extent of polymerization of denatured monomer, which decreases with increasing level of bound ligand. The bimodal thermogram observed for undefatted monomer persists upon simultaneous extrapolation of Td values to low concentration and low scan rate thereby demonstrating that this biphasic denaturation arising from ligand redistribution during denaturation is a true thermodynamic phenomenon and not an artifact of specific experimental conditions or the method used to induce denaturation. Study holds ProTherm entries: 5140 Extra Details: denatured monomer; cooperativity; long-chain fatty acid;,thermodynamic phenomenon

Submission Details

ID: etyr8erc

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:28 p.m.

Version: 1

Publication Details
Ross PD;Shrake A,J. Biol. Chem. (1988) Decrease in stability of human albumin with increase in protein concentration. PMID:3403521
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 PDB Entries

Structure ID Release Date Resolution Structure Title
1AO6 1997-07-18T00:00:00+0000 2.5 CRYSTAL STRUCTURE OF HUMAN SERUM ALBUMIN
1BJ5 1998-07-02T00:00:00+0000 2.5 HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID
1BKE 1998-07-06T00:00:00+0000 3.15 HUMAN SERUM ALBUMIN IN A COMPLEX WITH MYRISTIC ACID AND TRI-IODOBENZOIC ACID
1BM0 1998-07-28T00:00:00+0000 2.5 CRYSTAL STRUCTURE OF HUMAN SERUM ALBUMIN
1E78 2000-08-25T00:00:00+0000 2.6 Crystal structure of human serum albumin
1E7A 2000-08-26T00:00:00+0000 2.2 Crystal structure of human serum albumin complexed with the general anesthetic propofol
1E7B 2000-08-26T00:00:00+0000 2.38 Crystal structure of human serum albumin complexed with the general anesthetic halothane
1E7C 2000-08-26T00:00:00+0000 2.4 HUMAN SERUM ALBUMIN COMPLEXED WITH MYRISTIC ACID and the general anesthetic halothane
1E7E 2000-08-29T00:00:00+0000 2.5 HUMAN SERUM ALBUMIN COMPLEXED WITH DECANOIC ACID (CAPRIC ACID)
1E7F 2000-08-29T00:00:00+0000 2.43 HUMAN SERUM ALBUMIN COMPLEXED WITH DODECANOIC ACID (LAURIC ACID)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
93.7 Serum albumin Q28522 ALBU_MACMU
93.7 Serum albumin A2V9Z4 ALBU_MACFA
98.5 SERUM ALBUMIN Q5NVH5 ALBU_PONAB
100.0 SERUM ALBUMIN P02768 ALBU_HUMAN