The Crystal Structure of the Dachshund Domain of Human SnoN Reveals Flexibility in the Putative Protein Interaction Surface

Tomas Nyman,Martin Welin,Lari Lehtiö,Martin Hammarström,Camilla Persson,Pär Nordlund,Lionel Trésaugues,Susanne Flodin,Ida Johansson,Wenqing Xu

doi:10.1371/journal.pone.0012907

Tomas Nyman, Martin Welin + Show 8 more

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https://doi.org/10.1371/journal.pone.0012907

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Journal: PloS one	Publication Date: Sep 23, 2010
Citations: 28	License type: CC BY 4.0

Affiliation: Karolinska Institutet, Åbo Akademi University

Abstract

The human SnoN is an oncoprotein that interacts with several transcription-regulatory proteins such as the histone-deacetylase, N-CoR containing co-repressor complex and Smad proteins. This study presents the crystal structure of the Dachshund homology domain of human SnoN. The structure reveals a groove composed of conserved residues with characteristic properties of a protein-interaction surface. A comparison of the 12 monomers in the asymmetric unit reveals the presence of two major conformations: an open conformation with a well accessible groove and a tight conformation with a less accessible groove. The variability in the backbone between the open and the tight conformations matches the differences seen in previously determined structures of individual Dachshund homology domains, suggesting a general plasticity within this fold family. The flexibility observed in the putative protein binding groove may enable SnoN to recognize multiple interaction partners.Enhanced version This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

Highlights

The Ski and SnoN oncoproteins regulate gene expression through their interaction with a number of transcription factors such as Smads [1,2], retinoic acid receptor a (RARa) [3,4], and retinoblastoma protein [5]. They interact with transcriptional co-regulators such as the nuclear hormone receptor co-repressor (N-CoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT), both components of a macromolecular repressor complex containing mSin3 and histone deacetylase (HDAC) [6,7]
This study describes the crystal structure of the Dachshund homology domain of human SnoN
Overall description of the structure A fragment of human SnoN encompassing residues 137 to 238, covering the Dachshund homology domain (SnoN-DHD), was crystallized and diffraction data was collected to 2.45 A

Summary

Introduction

The Ski and SnoN oncoproteins regulate gene expression through their interaction with a number of transcription factors such as Smads [1,2], retinoic acid receptor a (RARa) [3,4], and retinoblastoma protein (pRb) [5]. Ski and SnoN share three structural domains, the N-terminal Dachshund homology domain (DHD), a Smad4-binding domain, and a C-terminal coiled-coil domain (Fig. 1A). Overall description of the structure A fragment of human SnoN encompassing residues 137 to 238, covering the Dachshund homology domain (SnoN-DHD), was crystallized and diffraction data was collected to 2.45 A .

Results

Conclusion