Document Detail


Structure of a yeast Dyn2-Nup159 complex and molecular basis for dynein light chain-nuclear pore interaction.
MedLine Citation:
PMID:  22411995     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The nuclear pore complex gates nucleocytoplasmic transport through a massive, eight-fold symmetric channel capped by a nucleoplasmic basket and structurally unique, cytoplasmic fibrils whose tentacles bind and regulate asymmetric traffic. The conserved Nup82 complex, composed of Nsp1, Nup82, and Nup159, forms the unique cytoplasmic fibrils that regulate mRNA nuclear export. Although the nuclear pore complex plays a fundamental, conserved role in nuclear trafficking, structural information about the cytoplasmic fibrils is limited. Here, we investigate the structural and biochemical interactions between Saccharomyces cerevisiae Nup159 and the nucleoporin, Dyn2. We find that Dyn2 is predominantly a homodimer and binds arrayed sites on Nup159, promoting the Nup159 parallel homodimerization. We present the first structure of Dyn2, determined at 1.85 Å resolution, complexed with a Nup159 target peptide. Dyn2 resembles homologous metazoan dynein light chains, forming homodimeric composite substrate binding sites that engage two independent 10-residue target motifs, imparting a β-strand structure to each peptide via antiparallel extension of the Dyn2 core β-sandwich. Dyn2 recognizes a highly conserved QT motif while allowing sequence plasticity in the flanking residues of the peptide. Isothermal titration calorimetric analysis of the comparative binding of Dyn2 to two Nup159 target sites shows similar affinities (18 and 13 μM), but divergent thermal binding modes. Dyn2 homodimers are arrayed in the crystal lattice, likely mimicking the arrayed architecture of Dyn2 on the Nup159 multivalent binding sites. Crystallographic interdimer interactions potentially reflect a cooperative basis for Dyn2-Nup159 complex formation. Our data highlight the determinants that mediate oligomerization of the Nup82 complex and promote a directed, elongated cytoplasmic fibril architecture.
Authors:
Erin M Romes; Ashutosh Tripathy; Kevin C Slep
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-07     Completed Date:  2012-07-30     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15862-73     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/4DS1
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MeSH Terms
Descriptor/Qualifier:
Acyltransferases / chemistry*,  genetics,  metabolism
Amino Acid Sequence
Binding Sites / genetics
Binding, Competitive
Calorimetry / methods
Crystallography, X-Ray
Dyneins / chemistry*,  genetics,  metabolism
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes / chemistry*,  genetics,  metabolism
Nuclear Pore / metabolism
Nuclear Pore Complex Proteins / chemistry*,  genetics,  metabolism
Protein Binding
Protein Multimerization
Protein Structure, Quaternary
Protein Structure, Secondary
Protein Structure, Tertiary
Saccharomyces cerevisiae Proteins / chemistry*,  genetics,  metabolism
Sequence Homology, Amino Acid
Grant Support
ID/Acronym/Agency:
1R01GM094415/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Multiprotein Complexes; 0/NUP159 protein, S cerevisiae; 0/Nuclear Pore Complex Proteins; 0/Saccharomyces cerevisiae Proteins; EC 2.3.-/Acyltransferases; EC 3.6.4.2/Dyneins; EC 3.6.4.2/SLC1 protein, S cerevisiae
Comments/Corrections

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