ARIA2: Automated NOE assignment and data integration in NMR structure calculation

Rieping, Wolfgang; Habeck, Michael; Bardiaux, Benjamin; Bernard, Aymeric; Malliavin, Thérèse E.; Nilges, Michaël

doi:10.1093/bioinformatics/btl589

Cited by 503 publications

(437 citation statements)

References 9 publications

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“…A small number of manually assigned seed NOE contacts (see SI Appendix, Fig. S1 and Table S1) are used as input to CYANA (20) or one of the other available automated NOESY assignment programs, such as AutoStructure (21), ARIA (22), or UNIO (23). The resulting, automatically assigned NOE distance restraints, along with backbone chemical shifts, RDC data, and the manually assigned seed restraints, are subsequently used within the RASREC CS-Rosetta protocol (18).…”

Section: Resultsmentioning

confidence: 99%

Determination of solution structures of proteins up to 40 kDa using CS-Rosetta with sparse NMR data from deuterated samples

Lange

Rossi

Sgourakis

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

202

232

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We have developed an approach for determining NMR structures of proteins over 20 kDa that utilizes sparse distance restraints obtained using transverse relaxation optimized spectroscopy experiments on perdeuterated samples to guide RASREC Rosetta NMR structure calculations. The method was tested on 11 proteins ranging from 15 to 40 kDa, seven of which were previously unsolved. The RASREC Rosetta models were in good agreement with models obtained using traditional NMR methods with larger restraint sets. In five cases X-ray structures were determined or were available, allowing comparison of the accuracy of the Rosetta models and conventional NMR models. In all five cases, the Rosetta models were more similar to the X-ray structures over both the backbone and side-chain conformations than the "best effort" structures determined by conventional methods. The incorporation of sparse distance restraints into RASREC Rosetta allows routine determination of high-quality solution NMR structures for proteins up to 40 kDa, and should be broadly useful in structural biology.nuclear magnetic resonance | sparse data | maltose binding protein | structural genomics | genetic algorithms A dvances in hardware, sample preparation, pulse sequence development, and refinement techniques have expanded the size and complexity of proteins accessible to structure determination by solution-state NMR to include proteins that, until recently, were exclusively the realm of X-ray crystallography (1-3). However, despite a number of landmark studies (4-7), only a small percentage of structures solved by NMR and deposited in the Protein Data Bank exceed 20 kDa in molecular weight. Larger structures need to be assembled by combining structural information from individual domains, and require additional techniques to elucidate the spatial arrangement, such as shape fitting (5) and/or paramagnetic restraints (8).The 20-kDa general limit coincides with the two fundamental problems in solution-state NMR: resonance overlap and progressive increase in the transverse relaxation rate (1∕T 2 ). As the size of a molecule increases, so does the rotational correlation time and, consequently, the efficiency of 1 H-1 H relaxation mechanisms. One way to suppress these effects is to incorporate deuterium into the protein sample, diluting the 1 H-1 H relaxation networks and increasing 13 C and 15 N relaxation times, resulting in sharper line widths and dramatic improvement of the signalto-noise ratios (2, 9, 10). Perdeuteration is generally required for studies of larger proteins (11-14), particularly membrane proteins (15, 16).Unfortunately, deuteration also eliminates the majority of 1 H-1 H NOEs, the main source of long-range distance information in solution-state NMR. Several methods have emerged for reintroducing protons at selected sites to function as distance probes in the structure (11,17). Methyl groups of isoleucine δ1, leucine, and valine side chains are straightforward to label with 13 C and 1 H isotopes in an otherwise deuterated protein sample (12, ...

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Section: Resultsmentioning

confidence: 99%

Determination of solution structures of proteins up to 40 kDa using CS-Rosetta with sparse NMR data from deuterated samples

Lange

Rossi

Sgourakis

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

202

232

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“…Hydrogen bond restraints for the backbone consistent with NOE patterns were also added. The structures were calculated using ARIA2.0 (18), assessed by PROCHECK (19), and displayed by MOLMOL (20). 15 N relaxation data were acquired using the standard pulse sequences (21).…”

Section: Methodsmentioning

confidence: 99%

Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)

Jiang

Xia

Yuan

et al. 2011

Journal of Biological Chemistry

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“…Additionally, a symmetric relative orientation of the two monomers is maintained by distance difference restraints between symmetry-related intermolecular C ␣ -C ␣ distances (38). Distance restraints from the CYANA calculationand TALOSϩ (39)-derived torsion angles and the residual dipolar coupling restraints were used in a water refinement calculation (40) with Aria 2.2 (41). The quality of the structure ensemble was validated using the iCING 3 web server as well as PROCHECK (43) and WHATCHECK (44).…”

mentioning

confidence: 99%

Structural Basis for Homodimerization of the Src-associated during Mitosis, 68-kDa Protein (Sam68) Qua1 Domain

Meyer

Tripsianes

Vincendeau

et al. 2010

Journal of Biological Chemistry

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Sam68 (Src-associated during mitosis, 68 kDa) is a prototypical member of the STAR (signal transducer and activator of RNA) family of RNA-binding proteins. STAR proteins bind mRNA targets and modulate cellular processes such as cell cycle regulation and tissue development in response to extracellular signals. Sam68 has been shown to modulate alternative splicing of the pre-mRNAs of CD44 and Bcl-xL, which are linked to tumor progression and apoptosis. Sam68 and other STAR proteins recognize bipartite RNA sequences and are thought to function as homodimers. However, the structural and functional roles of the self-association are not known. Here, we present the solution structure of the Sam68 Qua1 homodimerization domain. Each monomer consists of two antiparallel ␣-helices connected by a short loop. The two subunits are arranged perpendicular to each other in an unusual four-helix topology. Mutational analysis of Sam68 in vitro and in a cell-based assay revealed that the Qua1 domain and residues within the dimerization interface are essential for alternative splicing of a CD44 minigene. Together, our results indicate that the Qua1 homodimerization domain is required for regulation of alternative splicing by Sam68. Sam682 (Src-associated during mitosis, 68 kDa) (1) belongs to the STAR (signal transducer and activator of RNA) family of RNAbinding proteins, which also includes Qk1 (quaking 1), SF1 (splicing factor 1), and Gld-1 (germline development defective-1) (2). STAR family proteins link signaling pathways and many aspects of RNA metabolism (splicing, localization, and translation). They are regulated by post-translational modifications such as phosphorylation, acetylation, and arginine methylation (2).Sam68 acts in post-transcriptional regulation of pre-mRNA splicing in response to extracellular signals (3). It is involved in a variety of pathways, including insulin and T-cell receptor signaling (4), and plays a key role in cell cycle regulation (5). Sam68 exhibits binding specificity for homopolymeric poly(U) RNA and has been shown to recognize UAAA or UUUA sequences with high affinity as determined by Systematic Evolution of Ligands by EXponential Enrichment (SELEX) and in vivo crosslinking (6, 7). Post-translational modifications can regulate Sam68 function by critically affecting the accessibility to RNA (8, 9). Tyrosine phosphorylation by Src kinase during mitosis enhances the interaction of Sam68 with Ras-GAP (10) but prevents its association with RNA. On the other hand, acetylation of lysine residues by histone acetyltransferases enhances RNA binding (11). Finally, overexpression of Sam68 has been linked to prostate cancer, cell proliferation, and survival (12).Sam68 has been identified as a key determinant in the alternative splicing of various important RNA targets, like CD44 (13) and Bcl-x L (14), which are linked to apoptosis and cancer. In particular, alternative splicing of CD44 impacts embryonic development and immune response (15-18). Up to 10 variant exon sequences can be included in the mature C...

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ARIA2: Automated NOE assignment and data integration in NMR structure calculation

Abstract: A distribution with the source code of ARIA 2.1 is freely available at http://www.pasteur.fr/recherche/unites/Binfs/aria2.

Cited by 503 publications

References 9 publications

Determination of solution structures of proteins up to 40 kDa using CS-Rosetta with sparse NMR data from deuterated samples

Determination of solution structures of proteins up to 40 kDa using CS-Rosetta with sparse NMR data from deuterated samples

Interaction with Polyglutamine-expanded Huntingtin Alters Cellular Distribution and RNA Processing of Huntingtin Yeast Two-hybrid Protein A (HYPA)

Structural Basis for Homodimerization of the Src-associated during Mitosis, 68-kDa Protein (Sam68) Qua1 Domain

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