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Structural studies of Ets-1/Pax5 complex formation on DNA.
C W Garvie1, J Hagman, C Wolberger
1Department of Biophysics and Biophysical Chemistry, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Molecular Cell
|January 10, 2002
Summary
Pax5 protein aids Ets transcription factors in binding DNA for B cell gene expression. This interaction alters DNA binding, revealing a mechanism for combinatorial gene regulation.
Area of Science:
- Molecular Biology
- Genetics
- Structural Biology
Background:
- Pax5 is a key regulator of B cell development.
- Pax5 cooperates with Ets transcription factors to control gene expression.
- The mb-1 gene is crucial for B cell function.
Purpose of the Study:
- To elucidate the structural basis of Pax5-mediated recruitment of Ets proteins.
- To understand how Pax5 influences Ets protein DNA binding specificity.
- To reveal the molecular mechanism of combinatorial transcriptional regulation.
Main Methods:
- X-ray crystallography to determine the structure of Pax5 and Ets-1 bound to DNA.
- Structural comparison of Ets-1 bound to DNA with and without Pax5.
- Analysis of protein-DNA interactions.
Main Results:
- The crystal structure reveals how Pax5 selectively recruits different Ets proteins to the DNA binding site.
- Pax5 binding alters the specific DNA contacts made by the Ets-1 protein.
- Ets proteins bind poorly to the site alone but are recruited by Pax5.
Conclusions:
- Pax5 acts as a scaffold, facilitating Ets protein binding to DNA.
- Pax5 modifies Ets protein DNA recognition, enabling combinatorial control.
- This mechanism provides a general model for how transcription factors cooperate to regulate gene expression.