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1i2t

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Revision as of 11:07, 21 February 2008 by OCA (Talk | contribs)
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1i2t, resolution 1.04Å

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X-RAY STRUCTURE OF THE HUMAN HYPERPLASTIC DISCS PROTEIN: AN ORTHOLOG OF THE C-TERMINAL DOMAIN OF POLY(A)-BINDING PROTEIN

Contents

Overview

The poly(A)-binding protein (PABP) recognizes the 3' mRNA poly(A) tail and plays an essential role in eukaryotic translation initiation and mRNA stabilization/degradation. PABP is a modular protein, with four N-terminal RNA-binding domains and an extensive C terminus. The C-terminal region of PABP is essential for normal growth in yeast and has been implicated in mediating PABP homo-oligomerization and protein-protein interactions. A small, proteolytically stable, highly conserved domain has been identified within this C-terminal segment. Remarkably, this domain is also present in the hyperplastic discs protein (HYD) family of ubiquitin ligases. To better understand the function of this conserved region, an x-ray structure of the PABP-like segment of the human HYD protein has been determined at 1.04-A resolution. The conserved domain adopts a novel fold resembling a right-handed supercoil of four alpha-helices. Sequence profile searches and comparative protein structure modeling identified a small ORF from the Arabidopsis thaliana genome that encodes a structurally similar but distantly related PABP/HYD domain. Phylogenetic analysis of the experimentally determined (HYD) and homology modeled (PABP) protein surfaces revealed a conserved feature that may be responsible for binding to a PABP interacting protein, Paip1, and other shared interaction partners.

Disease

Known diseases associated with this structure: Cleft lip/palate, nonsyndromic OMIM:[142983], Hypodontia with orofacial cleft OMIM:[142983], Hypodontia, autosomal dominant OMIM:[142983], Witkop syndrome OMIM:[142983]

About this Structure

1I2T is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

X-ray structure of the human hyperplastic discs protein: an ortholog of the C-terminal domain of poly(A)-binding protein., Deo RC, Sonenberg N, Burley SK, Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4414-9. Epub 2001 Apr 3. PMID:11287654

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