The solution structure of the homeodomain of the rat insulin-gene enhancer protein Isl-1. Comparison with other homeodomains
(1999) In Journal of Molecular Biology 288(4). p.689-703- Abstract
- Homeodomains are one of the key families of eukaryotic DNA-binding motifs and provide an important model system for DNA recognition. We have determined a high-quality nuclear magnetic resonance (NMR) structure of the DNA-binding homeodomain of the insulin gene enhancer protein Isl-1 (Isl-1-HD). It forms the first solution structure of a homeodomain from the LIM family. It contains a well-defined inner core (residues 12–55) consisting of the classical three-helix structure observed in other homeodomains. The N terminus is unstructured up to residue 8, while the C terminus gradually becomes unstructured from residue 55 onwards. Some flexibility is evident in the loop parts of the inner core. Isl-1-HD has, despite its low sequence identity... (More)
- Homeodomains are one of the key families of eukaryotic DNA-binding motifs and provide an important model system for DNA recognition. We have determined a high-quality nuclear magnetic resonance (NMR) structure of the DNA-binding homeodomain of the insulin gene enhancer protein Isl-1 (Isl-1-HD). It forms the first solution structure of a homeodomain from the LIM family. It contains a well-defined inner core (residues 12–55) consisting of the classical three-helix structure observed in other homeodomains. The N terminus is unstructured up to residue 8, while the C terminus gradually becomes unstructured from residue 55 onwards. Some flexibility is evident in the loop parts of the inner core. Isl-1-HD has, despite its low sequence identity (23–34 %), a structure that is strikingly similar to that of the other homeodomains with known three-dimensional structures. Detailed analysis of Isl-1-HD and the other homeodomains rationalizes the differences in their temperature stability and explains the low stability of the Isl-1-HD in the free state (tm 22–30 °C). Upon DNA binding, a significant stabilization occurs (tm > 55 °C). The low stability of Isl-1-HD (and other mammalian homeodomains) suggests that in vivo Isl-1-HD recognizes its cognate DNA from its unfolded state. (Less)
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https://lup.lub.lu.se/record/ac440547-2c65-4a7b-82df-ab8fc2fb12ee
- author
- Ippel, Hans ; Larsson, Göran ; Behravan, Gity ; Zdunek, Janusz ; Lundqvist, Martin LU ; Schleucher, Jürgen ; Lycksell, Per-Olof and Wijmenga, Sybren
- publishing date
- 1999
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Molecular Biology
- volume
- 288
- issue
- 4
- pages
- 15 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:0032967237
- ISSN
- 1089-8638
- DOI
- 10.1006/jmbi.1999.2718
- language
- English
- LU publication?
- no
- id
- ac440547-2c65-4a7b-82df-ab8fc2fb12ee
- date added to LUP
- 2021-10-19 12:06:51
- date last changed
- 2022-03-19 03:45:22
@article{ac440547-2c65-4a7b-82df-ab8fc2fb12ee, abstract = {{Homeodomains are one of the key families of eukaryotic DNA-binding motifs and provide an important model system for DNA recognition. We have determined a high-quality nuclear magnetic resonance (NMR) structure of the DNA-binding homeodomain of the insulin gene enhancer protein Isl-1 (Isl-1-HD). It forms the first solution structure of a homeodomain from the LIM family. It contains a well-defined inner core (residues 12–55) consisting of the classical three-helix structure observed in other homeodomains. The N terminus is unstructured up to residue 8, while the C terminus gradually becomes unstructured from residue 55 onwards. Some flexibility is evident in the loop parts of the inner core. Isl-1-HD has, despite its low sequence identity (23–34 %), a structure that is strikingly similar to that of the other homeodomains with known three-dimensional structures. Detailed analysis of Isl-1-HD and the other homeodomains rationalizes the differences in their temperature stability and explains the low stability of the Isl-1-HD in the free state (<i>t</i><sub>m</sub> 22–30 °C). Upon DNA binding, a significant stabilization occurs (<i>t</i><sub>m</sub> > 55 °C). The low stability of Isl-1-HD (and other mammalian homeodomains) suggests that in vivo Isl-1-HD recognizes its cognate DNA from its unfolded state.}}, author = {{Ippel, Hans and Larsson, Göran and Behravan, Gity and Zdunek, Janusz and Lundqvist, Martin and Schleucher, Jürgen and Lycksell, Per-Olof and Wijmenga, Sybren}}, issn = {{1089-8638}}, language = {{eng}}, number = {{4}}, pages = {{689--703}}, publisher = {{Elsevier}}, series = {{Journal of Molecular Biology}}, title = {{The solution structure of the homeodomain of the rat insulin-gene enhancer protein Isl-1. Comparison with other homeodomains}}, url = {{http://dx.doi.org/10.1006/jmbi.1999.2718}}, doi = {{10.1006/jmbi.1999.2718}}, volume = {{288}}, year = {{1999}}, }