Atomically detailed description of the unfolding of alpha-lactalbumin by the combined use of experiments and simulations.


Abstract

The recombinant form of goat alpha-lactalbumin has a significantly faster unfolding rate compared to the authentic form, although the two molecules differ only in an extra methionine at the N terminus of the recombinant. The mechanism of the destabilization caused by this residue was investigated through the combined use of kinetic experiments and molecular dynamics simulations. Unfolding simulations for the authentic and recombinant forms at 398 K (ten trajectories of 5 ns for each form, 100 ns total) precisely reproduced the experimentally observed differences in unfolding behavior. In addition, experiments reproduced the destabilization of a mutant protein, T38A, faithfully as predicted by the simulations. This bidirectional verification between experiments and simulations enabled the atomically detailed description of the role of the extra methionine residue in the unfolding process. Study holds ProTherm entries: 19731, 19732, 19733, 19734, 19735, 19736, 19737, 19738 Extra Details: Authentic form equilibrium experiments; kinetic experiments; molecular dynamics simulations; protein unfolding; unfolding dynamics

Submission Details

ID: NAMfQwEz3

Submitter: Connie Wang

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

Version: 1

Publication Details
Oroguchi T;Ikeguchi M;Saeki K;Kamagata K;Sawano Y;Tanokura M;Kidera A;Kuwajima K,J. Mol. Biol. (2005) Atomically detailed description of the unfolding of alpha-lactalbumin by the combined use of experiments and simulations. PMID:16236317
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
3B0K 2012-06-13 1.6 Crystal structure of alpha-lactalbumin
1FKQ 2001-02-14 1.8 RECOMBINANT GOAT ALPHA-LACTALBUMIN T29V
6IP9 2019-02-20 1.85 Crystal Structure of Lanthanum ion (La3+) bound bovine alpha-lactalbumin
1FKV 2001-02-14 2.0 RECOMBINANT GOAT ALPHA-LACTALBUMIN T29I
1HMK 1999-11-26 2.0 RECOMBINANT GOAT ALPHA-LACTALBUMIN
1F6R 2000-12-13 2.2 CRYSTAL STRUCTURE OF APO-BOVINE ALPHA-LACTALBUMIN
1F6S 2000-12-13 2.2 CRYSTAL STRUCTURE OF BOVINE ALPHA-LACTALBUMIN
1HFZ 1997-07-29 2.3 ALPHA-LACTALBUMIN
2G4N 2007-02-20 2.3 Anomalous substructure of alpha-lactalbumin
1HFY 1997-07-07 2.3 ALPHA-LACTALBUMIN

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
94.4 Alpha-lactalbumin Q9TSR4 LALBA_BOSMU
95.1 Alpha-lactalbumin P00711 LALBA_BOVIN
96.5 Alpha-lactalbumin Q9TSN6 LALBA_BUBBU
97.9 Alpha-lactalbumin P09462 LALBA_SHEEP
100.0 Alpha-lactalbumin P00712 LALBA_CAPHI