Structural insights into the stability perturbations induced by N-terminal variation in human and goat α-lactalbumin

Protein Eng Des Sel. 2013 Feb;26(2):165-70. doi: 10.1093/protein/gzs093. Epub 2012 Nov 14.

Abstract

Addition of an extra methionine at the N-terminus by recombinant expression of α-lactalbumin in Escherichia coli significantly destabilizes the protein, and this destabilization has hampered mutational analyses such as the mutational phi-value analysis of the protein. Deletion of residue 1 from the recombinant form recovers the stability in human and goat α-lactalbumin. Here, we thus determined the crystal structures of the residue 1-deletion variants of recombinant human and goat α-lactalbumin, and compared the structures with those of the authentic and recombinant forms. The results demonstrate the importance of the N-terminal backbone structure and hydrogen-bonding pattern for the stability of α-lactalbumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Goats*
  • Humans
  • Hydrogen Bonding
  • Lactalbumin / chemistry*
  • Lactalbumin / genetics
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Mutagenesis, Site-Directed
  • Protein Stability
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Unfolding
  • Sequence Deletion
  • Thermodynamics

Substances

  • Lactalbumin