Solution Structure of the Symmetric Coiled Coil Tetramer Formed by the Oligomerization Domain of hnRNP C: Implications for Biological Function

Whitson, Stefanie R.; LeStourgeon, Wallace M.; Krezel, Andrzej M.

doi:10.1016/j.jmb.2005.05.002

Cited by 35 publications

(50 citation statements)

References 89 publications

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“…Chemical cross-linking was previously used to show that a short coiled-coil segment of hnRNP-C and the homologous region of Nab3 could multimerize (16,17). The 134-amino acid peptide was treated with increasing concentrations of bis(sulfosuccinimidyl) suberate, an amine-directed, bifunctional cross-linker, and separated on denaturing SDS-PAGE.…”

Section: A Conserved Region Of Nab3 Is Biologically Essential and Biomentioning

confidence: 99%

“…It contains a stretch of 16 glutamines adjacent to a short peptide that shares structural homology with an ␣-helix of the human hnRNP-C protein (15,16). Both elements of this "tail" region are involved in self-association, similar to the tetramerization helix of human hnRNP-C (17). Loss of either sequence component reduces the ability of Nab3 to support transcription termination (16).…”

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confidence: 99%

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A Network of Interdependent Molecular Interactions Describes a Higher Order Nrd1-Nab3 Complex Involved in Yeast Transcription Termination

Loya

O'Rourke

Degtyareva

et al. 2013

Journal of Biological Chemistry

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Background: How the yeast proteins Nrd1 and Nab3 provoke transcription termination is poorly understood. Results: An essential part of Nab3 contains a self-assembly domain that appears unstructured. Nrd1/Nab3 double mutants disrupt the function of this higher order complex, causing lethality. Conclusion: A large network of molecular interactions is needed for termination. Significance: A new essential function of Nab3 has been identified.

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Section: A Conserved Region Of Nab3 Is Biologically Essential and Biomentioning

confidence: 99%

mentioning

confidence: 99%

A Network of Interdependent Molecular Interactions Describes a Higher Order Nrd1-Nab3 Complex Involved in Yeast Transcription Termination

Loya

O'Rourke

Degtyareva

et al. 2013

Journal of Biological Chemistry

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“…The substitution of a single solvent-exposed glutamic acid residue (GLU20e to CYS) resulted in an antiparallel tetramer. PDB code 1TXP 25 corresponds to the oligomerization domain of the hnRNP antiparallel tetramer. Our model coiled coil contains the full length of the 1TXP peptide plus acetyl and N-methylamide caps, which shifts the numbering scheme by one compared with the PDB version.…”

Section: Model Systemsmentioning

confidence: 99%

“…Antiparallel coiled-coil tetramers such as the heterogeneous nuclear ribonucleoprotein (hnRNP) contain LEU, ILE, and VAL at the core positions, thus the packing effect will likely make only minor contributions in determining helix orientation. 25 A single substitution at a solvent-exposed site (GLU20eCYS) changed the topology of the tetrameric GCN4-LI peptide 5 from parallel to antiparallel. 24 An important structural feature in antiparallel coiled coils is the heptad register shift between neighboring helices.…”

Section: Introductionmentioning

confidence: 99%

Computational analysis of residue contributions to coiled‐coil topology

Torre

Lazaridis

2011

Protein Science

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A variety of features are thought to contribute to the oligomeric and topological specificity of coiled coils. In previous work, we examined the determinants of oligomeric state. Here, we examine the energetic basis for the tendency of six coiled-coil peptides to align their a-helices in antiparallel orientation using molecular dynamics simulations with implicit solvation (EEF1.1). We also examine the effect of mutations known to disrupt the topology of these peptides. In agreement with experiment, ARG or LYS at a or d positions were found to stabilize the antiparallel configuration. The modeling suggests that this is not due to a-a 0 or d-d 0 repulsions but due to interactions with e 0 and g 0 residues. TRP at core positions also favors the antiparallel configuration. Residues that disfavor parallel dimers, such as ILE at d, are better tolerated in, and thus favor the antiparallel configuration. Salt bridge networks were found to be more stabilizing in the antiparallel configuration for geometric reasons: antiparallel helices point amino acid side chains in opposite directions. However, the structure with the largest number of salt bridges was not always the most stable, due to desolvation and configurational entropy contributions. In tetramers, the extent of stabilization of the antiparallel topology by core residues is influenced by the e 0 residue on a neighboring helix. Residues at b and c positions in some cases also contribute to stabilization of antiparallel tetramers. This work provides useful rules toward the goal of designing coiled coils with a well-defined and predictable three-dimensional structure.

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“…While the endogenous hnRNP C protein acts as a (C1) 3 (C2) oligomer , it has been shown that C1 or C2 homotetramers retain the wild-type structural and functional properties (McAfee et al 1996b). The oligomerization is dependent on a central helical domain folding into antiparallel coiled-coil tetramers (Whitson et al 2005). Two hnRNP C subdomains are thought to be involved in RNA binding: The amino-terminal RNA recognition motif (RRM) recognizes five contiguous uridines, with the sequence stringency increasing gradually in the 5 ′ -3 ′ direction (Wan et al 2001;Cieniková et al 2014); a basic region preceding the oligomerization domain, rich in positively charged amino acids, provides additional, sequence-independent affinity for RNA (McAfee et al 1996a;Soltaninassab et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Evidence for cooperative tandem binding of hnRNP C RRMs in mRNA processing

Cieniková

Jayne

Damberger

et al. 2015

RNA

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The human hnRNP C is a ubiquitous cellular protein involved in mRNA maturation. Recently, we have shown that this protein specifically recognizes uridine (U) pentamers through its single RNA recognition motif (RRM). However, a large fraction of natural RNA targets of hnRNP C consists of much longer contiguous uridine stretches. To understand how these extended sites are recognized, we studied the binding of the RRM to U-tracts of 8-11 bases. In vivo investigation of internal translation activation of unr (upstream of N-ras) mRNA indicates that the conservation of the entire hnRNP C binding site, UC(U) 8 , is required for hnRNP C-dependent IRES activation. The assays further suggest a synergistic interplay between hnRNP C monomers, dependent on the protein's ability to oligomerize. In vitro spectroscopic and thermodynamic analyses show that isolated RRMs bind to (U) 11 oligomers as dimers. Structural modeling of a ternary double-RRM/RNA complex indicates additionally that two RRM copies can be accommodated on the canonical sequence UC(U) 8 . The proposed tandem RRM binding is in very good agreement with the transcriptome-wide recognition of extended U-tracts by full-length hnRNP C, which displays a cross-linking pattern consistent with a positively cooperative RRM dimer binding model.

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Solution Structure of the Symmetric Coiled Coil Tetramer Formed by the Oligomerization Domain of hnRNP C: Implications for Biological Function

Cited by 35 publications

References 89 publications

A Network of Interdependent Molecular Interactions Describes a Higher Order Nrd1-Nab3 Complex Involved in Yeast Transcription Termination

A Network of Interdependent Molecular Interactions Describes a Higher Order Nrd1-Nab3 Complex Involved in Yeast Transcription Termination

Computational analysis of residue contributions to coiled‐coil topology

Evidence for cooperative tandem binding of hnRNP C RRMs in mRNA processing

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