<i>ClusPro</i>: an automated docking and discrimination method for the prediction of protein complexes

Comeau, Stephen R.; Gatchell, David W.; Vajda, Sándor; Camacho, Carlos J.

doi:10.1093/bioinformatics/btg371

Cited by 814 publications

(708 citation statements)

References 30 publications

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“…The CAP-Gly/MT interface contacts determined by MAS NMR are consistent with those predicted by us using molecular docking in ClusPro (41). We used the recent cryo-EM structure of MTs (12) and our MAS NMR structure of CAP-Gly bound to MTs.…”

Section: Resultssupporting

confidence: 63%

Atomic-resolution structure of the CAP-Gly domain of dynactin on polymeric microtubules determined by magic angle spinning NMR spectroscopy

Yan

Guo

Hou

et al. 2015

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

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Microtubules and their associated proteins perform a broad array of essential physiological functions, including mitosis, polarization and differentiation, cell migration, and vesicle and organelle transport. As such, they have been extensively studied at multiple levels of resolution (e.g., from structural biology to cell biology). Despite these efforts, there remain significant gaps in our knowledge concerning how microtubule-binding proteins bind to microtubules, how dynamics connect different conformational states, and how these interactions and dynamics affect cellular processes. Structures of microtubule-associated proteins assembled on polymeric microtubules are not known at atomic resolution. Here, we report a structure of the cytoskeleton-associated protein glycine-rich (CAP-Gly) domain of dynactin motor on polymeric microtubules, solved by magic angle spinning NMR spectroscopy. We present the intermolecular interface of CAP-Gly with microtubules, derived by recording direct dipolar contacts between CAP-Gly and tubulin using double rotational echo double resonance (dREDOR)-filtered experiments. Our results indicate that the structure adopted by CAP-Gly varies, particularly around its loop regions, permitting its interaction with multiple binding partners and with the microtubules. To our knowledge, this study reports the first atomic-resolution structure of a microtubule-associated protein on polymeric microtubules. Our approach lays the foundation for atomic-resolution structural analysis of other microtubule-associated motors.magic angle spinning NMR | microtubules | dynactin's CAP-Gly domain | structure determination | intermolecular interface determination

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Section: Resultssupporting

confidence: 63%

Atomic-resolution structure of the CAP-Gly domain of dynactin on polymeric microtubules determined by magic angle spinning NMR spectroscopy

Yan

Guo

Hou

et al. 2015

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

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“…FlxR is in green; NrdI is in cyan with the 70s loop and ␣1* in blue, and the FMN (red) and FAD (magenta) cofactors are shown as sticks. The model was generated using ClusPro (66). B, electrostatic surface potential diagram of FlxR near the modeled interface with NrdI is shown contoured at Ϫ15 k B T (red) and ϩ15 kBT (blue).…”

Section: Discussionmentioning

confidence: 99%

Streptococcus sanguinis Class Ib Ribonucleotide Reductase

Makhlynets¹,

Boal

Rhodes

et al. 2014

Journal of Biological Chemistry

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Background: Class Ib ribonucleotide reductase (RNR) is an essential enzyme for aerobic growth of S. sanguinis. Results: Its manganese form is 3.5-fold more active than the iron form when assayed with NrdH and thioredoxin reductase. Conclusion: This specific activity is the highest reported to date for the class Ib RNR. Significance: Our studies suggest why manganese is important in streptococcal pathogenesis.

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“…SOS DH-PH-cat (molecule B in Protein Data Bank entry 1XD4) and SOS Histone (molecule E in PDB entry 1Q9C) were docked by using the ClusPro docking server (18,19) with the DOT algorithm [without electrostatics (20)] and the present default parameters. We followed the recommended default procedure in which 20,000 models were retained after initial docking and ranked based on desolvation energies and electrostatics.…”

Section: Methodsmentioning

confidence: 99%

“…We followed the recommended default procedure in which 20,000 models were retained after initial docking and ranked based on desolvation energies and electrostatics. The top 2,000 solutions were then clustered, and the clusters were ranked by using the ClusPro algorithm (19). In this procedure, the rank itself is the only metric provided for the quality of a solution because the clustering procedure removes a direct connection between a model and a scoring energy function.…”

Section: Methodsmentioning

confidence: 99%

Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless

Sondermann

Nagar

Bar–Sagi

et al. 2005

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

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The Ras-specific nucleotide exchange factor son of sevenless (SOS) is a large, multidomain protein with complex regulation, including a Ras-dependent allosteric mechanism. The N-terminal segment of SOS, the histone domain, contains two histone folds, which is highly unusual for a cytoplasmic protein. Using a combination of computational docking, small-angle x-ray scattering, mutagenesis, and calorimetry, we show that the histone domain folds into the rest of SOS and docks onto a helical linker that connects the pleckstrin-homology (PH) and Dbl-homology (DH) domains of SOS to the catalytic domain. In this model, a positively charged surface region on the histone domain is positioned so as to provide a fourth potential anchorage site on the membrane for SOS in addition to the PH domain, the allosteric Ras molecule, and the C-terminal adapter-binding site. The histone domain in SOS interacts with the helical linker, using a region of the surface that in nucleosomes is involved in histone tetramerization. Adjacent surface elements on the histone domain that correspond to the DNA-binding surface of nucleosomes form the predicted interaction site with the membrane. The orientation and position of the histone domain in the SOS model implicates it as a potential mediator of membrane-dependent activation signals.histone fold ͉ membrane interaction ͉ small-angle x-ray scattering ͉ signal transduction ͉ structure T he small G protein Ras is a cellular switch that cycles between an active GTP-bound state and an inactive GDP-bound state. GTP and GDP are both slow to dissociate from Ras, and the action of nucleotide exchange factors is critical for converting inactive Ras⅐GDP to the active Ras⅐GTP form (1). The activation of growth factor receptors in animal cell signaling results in the recruitment of the Ras-specific nucleotide exchange factor son of sevenless (SOS) to the plasma membrane, where it engages Ras and causes dissociation of bound nucleotide (2). The unregulated activation of Ras is a frequent hallmark of many cancers, a fact that underscores the importance of strict control of the nature of the nucleotide bound to Ras (3).SOS is a large protein (Ϸ1,300 residues; see Fig. 1 for a schematic diagram of its domain structure) that promotes nucleotide release by binding to Ras and opening up its active site (4). The Rem (Ras exchanger motif) and Cdc25 (named for the Ras activator protein in yeast) domains, located in the C-terminal half of SOS, are the minimal elements required for nucleotide exchange activity. The catalytic site of SOS, where nucleotide release from Ras occurs, is located entirely within the Cdc25 domain (4).We recently made the surprising discovery that Ras, which is the substrate of SOS, is itself required for SOS activity (5, 6). The binding of Ras⅐GTP to a distal site on the Cdc25 domain, bracketed by the Rem domain, stimulates nucleotide exchange activity. Perhaps more surprising was the realization that the binding of Ras⅐GDP to the distal allosteric site is required even for basal SOS activit...

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ClusPro: an automated docking and discrimination method for the prediction of protein complexes

Abstract: The fully automated docking and discrimination server ClusPro can be found at http://structure.bu.edu

Cited by 814 publications

References 30 publications

Atomic-resolution structure of the CAP-Gly domain of dynactin on polymeric microtubules determined by magic angle spinning NMR spectroscopy

Atomic-resolution structure of the CAP-Gly domain of dynactin on polymeric microtubules determined by magic angle spinning NMR spectroscopy

Streptococcus sanguinis Class Ib Ribonucleotide Reductase

Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless

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