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Title: Crystal Structure of Mouse Elf3 C-terminal DNA-binding Domain in Complex with Type II TGF-[beta] Receptor Promoter DNA

Abstract

The Ets family of transcription factors is composed of more than 30 members. One of its members, Elf3, is expressed in virtually all epithelial cells as well as in many tumors, including breast tumors. Several studies observed that the promoter of the type II TGF-{beta} receptor gene (T{beta}R-II) is strongly stimulated by Elf3 via two adjacent Elf3 binding sites, the A-site and the B-site. Here, we report the 2.2 {angstrom} resolution crystal structure of a mouse Elf3 C-terminal fragment, containing the DNA-binding Ets domain, in complex with the B-site of mouse type II TGF-{beta} receptor promoter DNA (mT{beta}R-II{sub DNA}). Elf3 contacts the core GGAA motif of the B-site from a major groove similar to that of known Ets proteins. However, unlike other Ets proteins, Elf3 also contacts sequences of the A-site from the minor groove of the DNA. DNA binding experiments and cell-based transcription studies indicate that minor groove interaction by Arg349 located in the Ets domain is important for Elf3 function. Equally interesting, previous studies have shown that the C-terminal region of Elf3, which flanks the Ets domain, is required for Elf3 binding to DNA. In this study, we determined that Elf3 amino acid residues within this flanking region,more » including Trp361, are important for the structural integrity of the protein as well as for the Efl3 DNA binding and transactivation activity.« less

Authors:
; ; ; ;  [1]
  1. Nebraska-Med
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1002474
Resource Type:
Journal Article
Journal Name:
J. Mol. Biol.
Additional Journal Information:
Journal Volume: 397; Journal Issue: (1) ; 03, 2010; Journal ID: ISSN 0022-2836
Country of Publication:
United States
Language:
ENGLISH
Subject:
36 MATERIALS SCIENCE; AMINO ACIDS; CRYSTAL STRUCTURE; DNA; GENES; MAMMARY GLANDS; NEOPLASMS; PROMOTERS; PROTEINS; RESIDUES; RESOLUTION; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Agarkar, Vinod B, Babayeva, Nigar D, Wilder, Phillip J, Rizzino, Angie, and Tahirov, Tahir H. Crystal Structure of Mouse Elf3 C-terminal DNA-binding Domain in Complex with Type II TGF-[beta] Receptor Promoter DNA. United States: N. p., 2010. Web. doi:10.1016/j.jmb.2010.01.017.
Agarkar, Vinod B, Babayeva, Nigar D, Wilder, Phillip J, Rizzino, Angie, & Tahirov, Tahir H. Crystal Structure of Mouse Elf3 C-terminal DNA-binding Domain in Complex with Type II TGF-[beta] Receptor Promoter DNA. United States. https://doi.org/10.1016/j.jmb.2010.01.017
Agarkar, Vinod B, Babayeva, Nigar D, Wilder, Phillip J, Rizzino, Angie, and Tahirov, Tahir H. 2010. "Crystal Structure of Mouse Elf3 C-terminal DNA-binding Domain in Complex with Type II TGF-[beta] Receptor Promoter DNA". United States. https://doi.org/10.1016/j.jmb.2010.01.017.
@article{osti_1002474,
title = {Crystal Structure of Mouse Elf3 C-terminal DNA-binding Domain in Complex with Type II TGF-[beta] Receptor Promoter DNA},
author = {Agarkar, Vinod B and Babayeva, Nigar D and Wilder, Phillip J and Rizzino, Angie and Tahirov, Tahir H},
abstractNote = {The Ets family of transcription factors is composed of more than 30 members. One of its members, Elf3, is expressed in virtually all epithelial cells as well as in many tumors, including breast tumors. Several studies observed that the promoter of the type II TGF-{beta} receptor gene (T{beta}R-II) is strongly stimulated by Elf3 via two adjacent Elf3 binding sites, the A-site and the B-site. Here, we report the 2.2 {angstrom} resolution crystal structure of a mouse Elf3 C-terminal fragment, containing the DNA-binding Ets domain, in complex with the B-site of mouse type II TGF-{beta} receptor promoter DNA (mT{beta}R-II{sub DNA}). Elf3 contacts the core GGAA motif of the B-site from a major groove similar to that of known Ets proteins. However, unlike other Ets proteins, Elf3 also contacts sequences of the A-site from the minor groove of the DNA. DNA binding experiments and cell-based transcription studies indicate that minor groove interaction by Arg349 located in the Ets domain is important for Elf3 function. Equally interesting, previous studies have shown that the C-terminal region of Elf3, which flanks the Ets domain, is required for Elf3 binding to DNA. In this study, we determined that Elf3 amino acid residues within this flanking region, including Trp361, are important for the structural integrity of the protein as well as for the Efl3 DNA binding and transactivation activity.},
doi = {10.1016/j.jmb.2010.01.017},
url = {https://www.osti.gov/biblio/1002474}, journal = {J. Mol. Biol.},
issn = {0022-2836},
number = (1) ; 03, 2010,
volume = 397,
place = {United States},
year = {Wed Aug 18 00:00:00 EDT 2010},
month = {Wed Aug 18 00:00:00 EDT 2010}
}