Structure of the N-terminal Mlp1-binding domain of the Saccharomyces cerevisiae mRNA-binding protein, Nab2 |
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Authors: | Grant Richard P Marshall Neil J Yang Ji-Chun Fasken Milo B Kelly Seth M Harreman Michelle T Neuhaus David Corbett Anita H Stewart Murray |
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Affiliation: | 1 MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK 2 Department of Biochemistry, Emory University School of Medicine, Rollins Research Center, Atlanta, GA, USA |
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Abstract: | Nuclear abundant poly(A) RNA-binding protein 2 (Nab2) is an essential yeast heterogeneous nuclear ribonucleoprotein that modulates both mRNA nuclear export and poly(A) tail length. The N-terminal domain of Nab2 (residues 1-97) mediates interactions with both the C-terminal globular domain of the nuclear pore-associated protein, myosin-like protein 1 (Mlp1), and the mRNA export factor, Gfd1. The solution and crystal structures of the Nab2 N-terminal domain show a primarily helical fold that is analogous to the PWI fold found in several other RNA-binding proteins. In contrast to other PWI-containing proteins, we find no evidence that the Nab2 N-terminal domain binds to nucleic acids. Instead, this domain appears to mediate protein:protein interactions that facilitate the nuclear export of mRNA. The Nab2 N-terminal domain has a distinctive hydrophobic patch centered on Phe73, consistent with this region of the surface being a protein:protein interaction site. Engineered mutations within this hydrophobic patch attenuate the interaction with the Mlp1 C-terminal domain but do not alter the interaction with Gfd1, indicating that this patch forms a crucial component of the interface between Nab2 and Mlp1. |
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Keywords: | Nab2, nuclear abundant poly(A) RNA-binding protein 2 Mlp1, myosin-like protein 1 NPC, nuclear pore complex hnRNP, heterogeneous nuclear ribonucleoprotein CT-Mlp1, C-terminal globular domain of Mlp1 GST, glutathione S-transferase rmsd, root-mean-square deviation NOE, nuclear Overhauser enhancement TLS, translation/libration/screw DBD, DNA-binding domain AD, activation domain PBS, phosphate-buffered saline EDTA, ethylenediaminetetraacetic acid HSQC, heteronuclear single quantum coherence NOESY, nuclear Overhauser enhancement spectroscopy PDB, Protein Data Bank |
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