High resolution structural studies of cro repressor protein and implications for dna recognition

D. H. Ohlendorf, W. F. Anderson, Y. Takeda, B. W. Matthews

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Cro repressor is a small dimeric protein that binds to specific sites on the DNA of bacterio-phage λ. The structure of Cro has been determined and suggests that the protein binds to its sequence-specific sites with a pair of two-fold related a-helices of the protein located within successive major grooves of the DNA. From the known three-dimensional structure of the repressor, model building and energy refinement have been used to develop a detailed model for the presumed complex between Cro and DNA. Recognition of specific DNA binding sites appears to occur via multiple hydrogen bonds between amino acid side chains of the protein and base pair atoms exposed within the major groove of DNA. The Cro:DNA model is consistent with the calculated electrostatic potential energy surface of the protein. From a series of amino acid sequence and gene sequence comparisons, it appears that a number of other DNA-binding proteins have an a-helical DNA-binding region similar to that seen in Cro. The apparent sequence homology includes not only DNA-binding proteins from different bacteriophages, but also gene-regulatory proteins from bacteria and yeast. It has also been found that the conformations of part of the presumed DNA-binding regions of Cro repressor, A. repressor and CAP gene activator proteins are strikingly similar. Taken together, these results strongly suggest that a two-helical structural unit occurs in the DNA-binding region of many proteins that regulate gene expression. However, the results to date do not suggest that there is a simple one-to-one recognition code between amino acids and bases. Crystals have been obtained of complexes of Cro with six-base-pair and nine-basepair DNA oligomers, and X-ray analysis of these co-crystals is in progress.

Original languageEnglish (US)
Pages (from-to)553-563
Number of pages11
JournalJournal of Biomolecular Structure and Dynamics
Volume1
Issue number2
DOIs
StatePublished - Oct 1983

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