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PMID: 12727888 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structural basis for the recognition of ldb1 by the N-terminal LIM domains of LMO2 and LMO4.

The EMBO journal ·Vol. 22 ·No. 9 ·2003-05-01 ·Pages 2224-33

Deane JE, Mackay JP, Kwan AH, Sum EY, Visvader JE, Matthews JM

Abstract

LMO2 and LMO4 are members of a small family of nuclear transcriptional regulators that are important for both normal development and disease processes. LMO2 is essential for hemopoiesis and angiogenesis, and inappropriate overexpression of this protein leads to T-cell leukemias. LMO4 is developmentally regulated in the mammary gland and has been implicated in breast oncogenesis. Both proteins comprise two tandemly repeated LIM domains. LMO2 and LMO4 interact with the ubiquitous nuclear adaptor protein ldb1/NLI/CLIM2, which associates with the LIM domains of LMO and LIM homeodomain proteins via its LIM interaction domain (ldb1-LID). We report the solution structures of two LMO:ldb1 complexes (PDB: 1M3V and 1J2O) and show that ldb1-LID binds to the N-terminal LIM domain (LIM1) of LMO2 and LMO4 in an extended conformation, contributing a third strand to a beta-hairpin in LIM1 domains. These findings constitute the first molecular definition of LIM-mediated protein-protein interactions and suggest a mechanism by which ldb1 can bind a variety of LIM domains that share low sequence homology.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Circular Dichroism DNA-Binding Proteins/metabolism Homeodomain Proteins/metabolism Inhibitor of Differentiation Protein 1 LIM Domain Proteins Metalloproteins/metabolism Models, Molecular Molecular Sequence Data Nuclear Magnetic Resonance, Biomolecular Protein Conformation Repressor Proteins Sequence Homology, Amino Acid Spectrophotometry, Ultraviolet Transcription Factors/chemistry,metabolism
Chemicals
Adaptor Proteins, Signal Transducing DNA-Binding Proteins Homeodomain Proteins Inhibitor of Differentiation Protein 1 LIM Domain Proteins LMO4 protein, human Metalloproteins Repressor Proteins Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Deane Janet E
School of Molecular and Microbial Biosciences, University of Sydney, NSW 2006, Australia.
Mackay Joel P
Kwan Ann H Y
Sum Eleanor Y M
Visvader Jane E
Matthews Jacqueline M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg196
Published
2003-05-01
Pages
2224-33
Language
English
Region
England
NLM ID
8208664
PMCID
PMC156068
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg196 PMC Full Text View journal details
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