LMO (LIM-only) and LIM-HD (LIM-homeodomain) proteins form a family of proteins that is required for myriad developmental processes and which can contribute to diseases such as T-cell leukaemia and breast cancer. The four LMO and 12 LIM-HD proteins in mammals are expressed in a combinatorial manner in many cell types, forming a transcriptional ‘LIM code’. The proteins all contain a pair of closely spaced LIM domains near their N-termini that mediate protein–protein interactions, including binding to the ∼30-residue LID (LIM interaction domain) of the essential co-factor protein Ldb1 (LIM domain-binding protein 1). In an attempt to understand the molecular mechanisms behind the LIM code, we have determined the molecular basis of binding of LMO and LIM-HD proteins for Ldb1LID through a series of structural, mutagenic and biophysical studies. These studies provide an explanation for why Ldb1 binds the LIM domains of the LMO/LIM-HD family, but not LIM domains from other proteins. The LMO/LIM-HD family exhibit a range of affinities for Ldb1, which influences the formation of specific functional complexes within cells. We have also identified an additional LIM interaction domain in one of the LIM-HD proteins, Isl1. Despite low sequence similarity to Ldb1LID, this domain binds another LIM-HD protein, Lhx3, in an identical manner to Ldb1LID. Through our and other studies, it is emerging that the multiple layers of competitive binding involving LMO and LIM-HD proteins and their partner proteins contribute significantly to cell fate specification and development.
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December 2008
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Conference Article|
November 19 2008
Competition between LIM-binding domains
Jacqueline M. Matthews;
Jacqueline M. Matthews
1
1School of Molecular and Microbial Biosciences, The University of Sydney, NSW 2006, Australia
1To whom correspondence should be addressed (email j.matthews@usyd.edu.au).
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Mugdha Bhati;
Mugdha Bhati
1School of Molecular and Microbial Biosciences, The University of Sydney, NSW 2006, Australia
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Vanessa J. Craig;
Vanessa J. Craig
1School of Molecular and Microbial Biosciences, The University of Sydney, NSW 2006, Australia
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Janet E. Deane;
Janet E. Deane
1School of Molecular and Microbial Biosciences, The University of Sydney, NSW 2006, Australia
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Cy Jeffries;
Cy Jeffries
1School of Molecular and Microbial Biosciences, The University of Sydney, NSW 2006, Australia
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Christopher Lee;
Christopher Lee
1School of Molecular and Microbial Biosciences, The University of Sydney, NSW 2006, Australia
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Amy L. Nancarrow;
Amy L. Nancarrow
1School of Molecular and Microbial Biosciences, The University of Sydney, NSW 2006, Australia
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Daniel P. Ryan;
Daniel P. Ryan
1School of Molecular and Microbial Biosciences, The University of Sydney, NSW 2006, Australia
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Margaret Sunde
Margaret Sunde
1School of Molecular and Microbial Biosciences, The University of Sydney, NSW 2006, Australia
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Publisher: Portland Press Ltd
Received:
August 08 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (6): 1393–1397.
Article history
Received:
August 08 2008
Citation
Jacqueline M. Matthews, Mugdha Bhati, Vanessa J. Craig, Janet E. Deane, Cy Jeffries, Christopher Lee, Amy L. Nancarrow, Daniel P. Ryan, Margaret Sunde; Competition between LIM-binding domains. Biochem Soc Trans 1 December 2008; 36 (6): 1393–1397. doi: https://doi.org/10.1042/BST0361393
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