Alternatively folded states of an immunoglobulin.


Abstract

Well-defined, non-native protein structures of low stability have been increasingly observed as intermediates in protein folding or as equilibrium structures populated under specific solvent conditions. These intermediate structures, frequently referred to as molten globule states, are characterized by the presence of secondary structure, a lack of significant tertiary contacts, increased hydrophobicity and partial specific volume as compared to native structures, and low cooperativity in thermal unfolding. The present study demonstrates that under acidic conditions (pH less than 3) the antibody MAK33 can assume a folded stable conformation. This A-state is characterized by a high degree of secondary structure, increased hydrophobicity, a native-like maximum wavelength of fluorescence emission, and a tendency toward slow aggregation. A prominent feature of this low-pH conformation is the stability against denaturant and thermal unfolding that is manifested in highly cooperative reversible phase transitions indicative of the existence of well-defined tertiary contacts. These thermodynamic results are corroborated by the kinetics of folding from the completely unfolded chain to the alternatively folded state at pH 2. The given data suggest that MAK33 at pH 2 adopts a cooperative structure that differs from the native immunoglobulin fold at pH 7. This alternatively folded state exhibits certain characteristics of the molten globule but differs distinctly from it by its extraordinary structural stability that is characteristic for native protein structures. Study holds ProTherm entries: 3974, 3975, 3976 Extra Details:

Submission Details

ID: JVQ3yuXL3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:23 p.m.

Version: 1

Publication Details
Buchner J;Renner M;Lilie H;Hinz HJ;Jaenicke R;Kiefhabel T;Rudolph R,Biochemistry (1991) Alternatively folded states of an immunoglobulin. PMID:1906346
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
15C8 1998-03-18T00:00:00+0000 2.5 CATALYTIC ANTIBODY 5C8, FREE FAB
1A0Q 1997-12-05T00:00:00+0000 2.3 29G11 COMPLEXED WITH PHENYL [1-(1-N-SUCCINYLAMINO)PENTYL] PHOSPHONATE
1A3L 1998-01-22T00:00:00+0000 1.95 CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION
1ACY 1994-02-10T00:00:00+0000 3.0 CRYSTAL STRUCTURE OF THE PRINCIPAL NEUTRALIZING SITE OF HIV-1
1C12 1999-07-20T00:00:00+0000 2.6 INSIGHT IN ODORANT PERCEPTION: THE CRYSTAL STRUCTURE AND BINDING CHARACTERISTICS OF ANTIBODY FRAGMENTS DIRECTED AGAINST THE MUSK ODORANT TRASEOLIDE
1CIC 1999-03-31T00:00:00+0000 2.5 IDIOTOPE-ANTI-IDIOTOPE FAB-FAB COMPLEX; D1.3-E225
1CK0 1999-04-26T00:00:00+0000 2.5 ANTI-ANTI-IDIOTYPIC ANTIBODY AGAINST HUMAN ANGIOTENSIN II, UNLIGANDED FORM
1CL7 1999-05-06T00:00:00+0000 3.0 ANTI HIV1 PROTEASE FAB
1IGY 1997-10-09T00:00:00+0000 3.2 STRUCTURE OF IMMUNOGLOBULIN
1JRH 1997-09-23T00:00:00+0000 2.8 COMPLEX (ANTIBODY/ANTIGEN)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Ig gamma-1 chain C region secreted form P01869 IGH1M_MOUSE
100.0 Ig gamma-1 chain C region secreted form P01868 IGHG1_MOUSE