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 LIM Domain | |
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Structure:
 The LIM domain is a cysteine and histidine rich, zinc-coordinating domain composed of two tandemly repeated zinc fingers. The domain consists of two orthogonally arranged antiparallel beta-sheets with the carboxy-terminal zinc finger motif terminated by an alpha helix. The two zinc fingers pack together via a hydrophobic interface formed by conservatively substituted residues. Several different LIM domain structures have been solved. The three dimensional NMR structure of the second LIM domain from quail CRP2 is depicted as a representative example. The two tetrahedrally coordinated zinc ions are shown in black.
Structure Reference:
Konrat, R. et al. (1997) J. Biol. Chem. 272(18): 12001-12007. PDB: 1QLI.
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Domain binding and function:
The LIM domain was first identified in three developmentally regulated transcription factors Lin-1, Isl-1, and Mec-3. It consists of approximately 60 amino acids and has been identified in over 300 proteins from organisms ranging from yeast to humans. The LIM domain is a zinc binding, cysteine rich motif consisting of two tandemly repeated zinc fingers. Classically, the LIM consensus sequence has been defined as CX2CX16 – 23HX2CX2CX2CX16 – 21 CX2(CH/D) with a highly variable sequence in the remainder of the domain conferring functional specificity. Unlike GATA type zinc fingers, LIM domains do not seem to bind DNA but instead appear to mediate protein-protein interactions. Functionally, LIM domain containing proteins have diverse cellular roles as regulators of gene expression, cell adhesion, cell motility and signal transduction. Some LIM-domain containing proteins appear to function solely as adapters to bring together other components into a complex (ie LMO and CRP) while other LIM domain containing proteins clearly have other functions conferred by additional functional domains such as the DNA binding homeodomain or a catalytic kinase domain. In addition, certain LIM domains have been observed to form dimers with other LIM domains.
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Examples of Proteins:
| LIM domain protein |
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Binding partner |
LIM domain binding site |
| Enigma |  |
Insulin receptor via third LIM domain of Enigma |
tyrosine-containing tight turn in Insulin receptor |
| Enigma | |
Ret receptor via second LIM domain of Enigma |
AKLY motif of Ret receptor |
| PINCH | |
Integrin linked kinase (ILK) via first LIM domain of PINCH |
ANK repeat region of ILK |
PINCH
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NCK2 (4th LIM Domain)
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| hCRP | |
hCRP via LIM domains |
LIM domain homo-dimerization |
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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