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A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions.

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A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions. / Gadd, Morgan Stuart; Jacques, David A; Nisevic, Ivan et al.
In: Journal of Biological Chemistry, Vol. 228, 26.07.2013, p. 21924-21935.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Gadd, MS, Jacques, DA, Nisevic, I, Craig, VJ, Kwan, AH, Guss, JM & Matthews, JM 2013, 'A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions.', Journal of Biological Chemistry, vol. 228, pp. 21924-21935. https://doi.org/10.1074/jbc.M113.478586

APA

Gadd, M. S., Jacques, D. A., Nisevic, I., Craig, V. J., Kwan, A. H., Guss, J. M., & Matthews, J. M. (2013). A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions. Journal of Biological Chemistry, 228, 21924-21935. https://doi.org/10.1074/jbc.M113.478586

Vancouver

Gadd MS, Jacques DA, Nisevic I, Craig VJ, Kwan AH, Guss JM et al. A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions. Journal of Biological Chemistry. 2013 Jul 26;228:21924-21935. Epub 2013 Jun 9. doi: 10.1074/jbc.M113.478586

Author

Gadd, Morgan Stuart ; Jacques, David A ; Nisevic, Ivan et al. / A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions. In: Journal of Biological Chemistry. 2013 ; Vol. 228. pp. 21924-21935.

Bibtex

@article{c8736890f94a4661995c523d4849e325,
title = "A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions.",
abstract = "Islet 1 (Isl1) is a transcription factor of the LIM-homeodomain (LIM-HD) protein family and is essential for many developmental processes. LIM-HD proteins all contain two protein-interacting LIM domains, a DNA-binding homeodomain (HD), and a C-terminal region. In Isl1, the C-terminal region also contains the LIM homeobox 3 (Lhx3)-binding domain (LBD), which interacts with the LIM domains of Lhx3. The LIM domains of Isl1 have been implicated in inhibition of DNA binding potentially through an intramolecular interaction with or close to the HD. Here we investigate the LBD as a candidate intramolecular interaction domain. Competitive yeast-two hybrid experiments indicate that the LIM domains and LBD from Isl1 can interact with apparently low affinity, consistent with no detection of an intermolecular interaction in the same system. Nuclear magnetic resonance studies show that the interaction is specific, whereas substitution of the LBD with peptides of the same amino acid composition but different sequence is not specific. We solved the crystal structure of a similar but higher affinity complex between the LIM domains of Isl1 and the LIM interaction domain from the LIM-HD cofactor protein LIM domain-binding protein 1 (Ldb1) and used these coordinates to generate a homology model of the intramolecular interaction that indicates poorer complementarity for the weak intramolecular interaction. The intramolecular interaction in Isl1 may provide protection against aggregation, minimize unproductive DNA binding, and facilitate cofactor exchange within the cell.",
author = "Gadd, {Morgan Stuart} and Jacques, {David A} and Ivan Nisevic and Craig, {Vanessa J} and Kwan, {Ann H} and Guss, {J Mitchell} and Matthews, {Jacqueline M}",
year = "2013",
month = jul,
day = "26",
doi = "10.1074/jbc.M113.478586",
language = "English",
volume = "228",
pages = "21924--21935",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",

}

RIS

TY - JOUR

T1 - A structural basis for the regulation of the LIM-homeodomain protein islet 1 (Isl1) by intra- and intermolecular interactions.

AU - Gadd, Morgan Stuart

AU - Jacques, David A

AU - Nisevic, Ivan

AU - Craig, Vanessa J

AU - Kwan, Ann H

AU - Guss, J Mitchell

AU - Matthews, Jacqueline M

PY - 2013/7/26

Y1 - 2013/7/26

N2 - Islet 1 (Isl1) is a transcription factor of the LIM-homeodomain (LIM-HD) protein family and is essential for many developmental processes. LIM-HD proteins all contain two protein-interacting LIM domains, a DNA-binding homeodomain (HD), and a C-terminal region. In Isl1, the C-terminal region also contains the LIM homeobox 3 (Lhx3)-binding domain (LBD), which interacts with the LIM domains of Lhx3. The LIM domains of Isl1 have been implicated in inhibition of DNA binding potentially through an intramolecular interaction with or close to the HD. Here we investigate the LBD as a candidate intramolecular interaction domain. Competitive yeast-two hybrid experiments indicate that the LIM domains and LBD from Isl1 can interact with apparently low affinity, consistent with no detection of an intermolecular interaction in the same system. Nuclear magnetic resonance studies show that the interaction is specific, whereas substitution of the LBD with peptides of the same amino acid composition but different sequence is not specific. We solved the crystal structure of a similar but higher affinity complex between the LIM domains of Isl1 and the LIM interaction domain from the LIM-HD cofactor protein LIM domain-binding protein 1 (Ldb1) and used these coordinates to generate a homology model of the intramolecular interaction that indicates poorer complementarity for the weak intramolecular interaction. The intramolecular interaction in Isl1 may provide protection against aggregation, minimize unproductive DNA binding, and facilitate cofactor exchange within the cell.

AB - Islet 1 (Isl1) is a transcription factor of the LIM-homeodomain (LIM-HD) protein family and is essential for many developmental processes. LIM-HD proteins all contain two protein-interacting LIM domains, a DNA-binding homeodomain (HD), and a C-terminal region. In Isl1, the C-terminal region also contains the LIM homeobox 3 (Lhx3)-binding domain (LBD), which interacts with the LIM domains of Lhx3. The LIM domains of Isl1 have been implicated in inhibition of DNA binding potentially through an intramolecular interaction with or close to the HD. Here we investigate the LBD as a candidate intramolecular interaction domain. Competitive yeast-two hybrid experiments indicate that the LIM domains and LBD from Isl1 can interact with apparently low affinity, consistent with no detection of an intermolecular interaction in the same system. Nuclear magnetic resonance studies show that the interaction is specific, whereas substitution of the LBD with peptides of the same amino acid composition but different sequence is not specific. We solved the crystal structure of a similar but higher affinity complex between the LIM domains of Isl1 and the LIM interaction domain from the LIM-HD cofactor protein LIM domain-binding protein 1 (Ldb1) and used these coordinates to generate a homology model of the intramolecular interaction that indicates poorer complementarity for the weak intramolecular interaction. The intramolecular interaction in Isl1 may provide protection against aggregation, minimize unproductive DNA binding, and facilitate cofactor exchange within the cell.

U2 - 10.1074/jbc.M113.478586

DO - 10.1074/jbc.M113.478586

M3 - Journal article

VL - 228

SP - 21924

EP - 21935

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

ER -