NDLI: Retroevolution of λ Cro toward a stable monomer

Content Provider	PubMed Central
Author	Lefevre, Kelly R. Cordes, Matthew H. J.
Copyright Year	2003
Abstract	The Cro protein from bacteriophage λ has a dimeric α+β fold that evolved from an ancestral all-α monomer. The sequence mutations responsible for this dramatic structural evolution are unknown. Here we use analysis of sequence alignments to show that Ala-33, a small side chain in the hydrophobic “ball-and-socket” dimer interface of λ Cro, was a much larger tryptophan side chain at a previous point in evolution. The retroevolutionary λ Cro-A33W mutant shows a 10-fold reduction in dimerization affinity relative to the wild type as well as a large increase in monomer thermal stability (ΔT m > 10°C), apparently due to partial filling of the hydrophobic socket from within the same monomer. An additional mutation in the dimer interface, F58D, almost completely abolishes detectable dimerization while maintaining the high monomer stability. The secondary structure content of the monomerized versions of λ Cro is similar to that of the wild-type protein, and the tertiary structure of the monomer appears relatively well defined. These results (i) support a model in which the ball-and-socket dimer interface of λ Cro was created by altered volume mutations within a limited branch of the Cro lineage and (ii) suggest the possibility that the evolution of the α+β dimer from an all-α monomer proceeded through an α+β monomer intermediate.
Related Links	http://dx.doi.org/10.1073/pnas.0537925100
Ending Page	2350
Page Count	6
Starting Page	2345
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	100
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2003-03-04
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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