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Related Experiment Videos

Retroevolution of lambda Cro toward a stable monomer.

Kelly R LeFevre1, Matthew H J Cordes

  • 1Department of Biochemistry and Molecular Biophysics, University of Arizona, Tucson, AZ 85721-0088, USA.

Proceedings of the National Academy of Sciences of the United States of America
|February 25, 2003
PubMed
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Researchers retroevolved lambda Cro protein mutations, revealing Ala-33 was once a larger tryptophan. This uncovered insights into protein structural evolution and dimer interface changes.

Area of Science:

  • Protein evolution
  • Structural biology
  • Bioinformatics

Background:

  • The Cro protein of bacteriophage lambda possesses a dimeric alpha+beta fold.
  • Its evolutionary path from an ancestral all-alpha monomer is not fully understood.
  • Key sequence mutations driving this structural transformation remain unidentified.

Purpose of the Study:

  • To investigate the sequence mutations responsible for the structural evolution of lambda Cro protein.
  • To understand the role of specific amino acid residues in dimer interface formation and stability.
  • To explore the evolutionary trajectory from an all-alpha monomer to an alpha+beta dimer.

Main Methods:

  • Analysis of sequence alignments to infer ancestral protein states.
  • Site-directed mutagenesis to create retroevolutionary lambda Cro variants (e.g., A33W).

Related Experiment Videos

  • Biophysical assays to measure dimerization affinity and monomer thermal stability (Delta T(m)).

    • Main Results:

    • Identified Ala-33 in the wild-type lambda Cro dimer interface as a retroevolutionary tryptophan.
    • The lambda Cro-A33W mutant exhibited a 10-fold decrease in dimerization affinity and increased monomer stability (>10°C).
    • An additional mutation (F58D) nearly eliminated dimerization while preserving monomer stability, with well-defined monomer structures.

    Conclusions:

    • The ball-and-socket dimer interface of lambda Cro likely arose from altered volume mutations within its lineage.
    • Protein evolution may involve an alpha+beta monomer intermediate during the transition from an all-alpha monomer to an alpha+beta dimer.
    • Specific mutations can significantly impact protein dimerization and stability, offering insights into evolutionary mechanisms.