Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The solution structure of the homeodomain of the rat insulin-gene enhancer protein Isl-1. Comparison with other homeodomains

Ippel, Hans ; Larsson, Göran ; Behravan, Gity ; Zdunek, Janusz ; Lundqvist, Martin LU ; Schleucher, Jürgen ; Lycksell, Per-Olof and Wijmenga, Sybren (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)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
publishing date
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> &gt; 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}},
}