HADDOCK versus HADDOCK: New features and performance of HADDOCK2.0 on the CAPRI targets

Vries, Sjoerd J. de; Dijk, Aalt D.J. van; Krzeminski, Mickaël; Dijk, Mark van; Thureau, Aurélien; Hsu, Victor L.; Wassenaar, Tsjerk A.; Bonvin, Alexandre M. J. J.

doi:10.1002/prot.21723

Cited by 530 publications

(571 citation statements)

References 42 publications

(58 reference statements)

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“…Docking of hCXCL1-Heparin Complexes-Molecular docking of heparin oligosaccharides to hCXCL1 WT and the R8A dimer was carried out using high ambiguity driven biomolecular docking (HADDOCK) (24,25), as described previously for the CXCL8-heparin complexes (26). We used the hCXCL1 dimer (PDB code 1MGS) and dp8-and dp14-mer structures generated from a heparin 12-mer (PDB code 1HPN) as the starting structures (19,27).…”

Section: Methodsmentioning

confidence: 99%

CXCL1/MGSA Is a Novel Glycosaminoglycan (GAG)-binding Chemokine

Sepuru

Rajarathnam

2016

Journal of Biological Chemistry

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In humans, the chemokine CXCL1/MGSA (hCXCL1) plays fundamental and diverse roles in pathophysiology, from microbial killing to cancer progression, by orchestrating the directed migration of immune and non-immune cells. Cellular trafficking is highly regulated and requires concentration gradients that are achieved by interactions with sulfated glycosaminoglycans (GAGs). However, very little is known regarding the structural basis underlying hCXCL1-GAG interactions. We addressed this by characterizing the binding of GAG heparin oligosaccharides to hCXCL1 using NMR spectroscopy. Binding experiments under conditions at which hCXCL1 exists as monomers and dimers indicate that the dimer is the high-affinity GAG ligand. NMR experiments and modeling studies indicate that lysine and arginine residues mediate binding and that they are located in two non-overlapping domains. One domain, consisting of N-loop and C-helical residues (defined as ␣-domain) has also been identified previously as the GAG-binding domain for the related chemokine CXCL8/IL-8. The second domain, consisting of residues from the N terminus, 40s turn, and third ␤-strand (defined as ␤-domain) is novel. Eliminating ␤-domain binding by mutagenesis does not perturb ␣-domain binding, indicating two independent GAG-binding sites. It is known that N-loop and N-terminal residues mediate receptor activation, and we show that these residues are also involved in extensive GAG interactions. We also show that the GAG-bound hCXCL1 completely occlude receptor binding. We conclude that hCXCL1-GAG interactions provide stringent control over regulating chemokine levels and receptor accessibility and activation, and that chemotactic gradients mediate cellular trafficking to the target site.Chemokines, a large family of small soluble proteins, are highly versatile and play fundamental roles in diverse functions, from combating infection and initiating tissue repair to regulating metabolism and organ development (1, 2). Common to these various functions is the directed movement of various cell types to distal and remote locations. Cellular trafficking must be highly coordinated to elicit the required biological function, and its dysregulation could be detrimental, resulting in disease. There is now increasing evidence that the ability of a chemokine to reversibly exist as monomers and dimers and binding glycosaminoglycans is coupled and plays important roles in mediating these functions (3, 4).Glycosaminoglycans (GAGs) 2 such as heparan sulfate (HS) are highly sulfated polysaccharides. They are expressed ubiquitously by many cell types, are anchored to the cell surface by covalent attachment to membrane proteins, and form non-covalent complexes with proteins in the extracellular matrix (5-7). Animal models and cellular studies have established that GAG interactions dictate chemokine concentration gradients and that these gradients orchestrate cellular trafficking (8 -10). GAGs are acidic, and chemokines are basic or contain clusters of basic residues, indicating that electr...

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Section: Methodsmentioning

confidence: 99%

CXCL1/MGSA Is a Novel Glycosaminoglycan (GAG)-binding Chemokine

Sepuru

Rajarathnam

2016

Journal of Biological Chemistry

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“…The docking simulations were performed using the HADDOCK web server (37) (http://haddock.science.uu.nl/ services/HADDOCK). The HDX-MS information was mapped onto KaiB and KaiC solvent-accessible surfaces, resulting in two lists of active residues used to derive ambiguous interaction restraints (55).…”

Section: Hdx-msmentioning

confidence: 99%

Insight into cyanobacterial circadian timing from structural details of the KaiB–KaiC interaction

Snijder

Burnley

Wiegard

et al. 2014

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

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Significance The Kai system is a widely studied model in theoretical biology and systems biology. It is to date the only known circadian clock that can be reconstituted in vitro. Essential to the rhythmicity of the system is the formation of the KaiC–KaiB complex. Many aspects of this interaction, such as the mode of binding of KaiB, the stoichiometry of the interaction, and the exact binding interfaces have long remained ambiguous. We present a mass spectrometry-based structural model of the KaiC–KaiB interaction that answers many of these outstanding questions on the basis of direct experimental evidence. This structural model sheds light on the intricate workings of the in vitro oscillator.

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“…Docking studies between LRR and NB-ARC were performed with HADDOCK in conjunction with CNS due to the facilities this module has in using constraints and its high score obtained in the CAPRI evaluation (Dominguez et al, 2003;van Dijk et al, 2005;de Vries et al, 2007). All the docking was performed according to the following protocol.…”

Section: Internal Model Assessmentmentioning

confidence: 99%

Structural Determinants at the Interface of the ARC2 and Leucine-Rich Repeat Domains Control the Activation of the Plant Immune Receptors Rx1 and Gpa2

et al. 2013

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Many plant and animal immune receptors have a modular nucleotide-binding-leucine-rich repeat (NB-LRR) architecture in which a nucleotide-binding switch domain, NB-ARC, is tethered to a LRR sensor domain. The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly understood. Here, we report structural determinants governing the interaction between the NB-ARC and LRR in the highly homologous plant immune receptors Gpa2 and Rx1, which recognize the potato cyst nematode Globodera pallida and Potato virus X, respectively. Systematic shuffling of polymorphic sites between Gpa2 and Rx1 showed that a minimal region in the ARC2 and N-terminal repeats of the LRR domain coordinate the activation state of the protein. We identified two closely spaced amino acid residues in this region of the ARC2 (positions 401 and 403) that distinguish between autoactivation and effector-triggered activation. Furthermore, a highly acidic loop region in the ARC2 domain and basic patches in the N-terminal end of the LRR domain were demonstrated to be required for the physical interaction between the ARC2 and LRR. The NB-ARC and LRR domains dissociate upon effector-dependent activation, and the complementary-charged regions are predicted to mediate a fast reassociation, enabling multiple rounds of activation. Finally, we present a mechanistic model showing how the ARC2, NB, and N-terminal half of the LRR form a clamp, which regulates the dissociation and reassociation of the switch and sensor domains in NB-LRR proteins.Resistance (R) proteins play a central role in the recognition-based immune system of plants. Unlike vertebrates, plants lack an adaptive immune system with highly specialized immune cells. Instead, they rely on an innate immune system in which each cell is autonomous. Two types of immune receptors can be distinguished in plants, pathogen-associated molecular patterns recognition receptors that detect conserved molecular patterns in plant pathogens and intracellular R proteins that recognize specific effectors employed by pathogens as modifiers of host metabolism or defense mechanisms (Jones and Dangl, 2006). Effector-triggered activation of R proteins leads to an array of protective responses, often culminating in programmed cell death at the site of infection (Greenberg and Yao, 2004), thereby preventing further ingress of the pathogen. Pathogens have evolved mechanisms to evade recognition by R proteins and to regain their virulence (Dodds and Rathjen, 2010). This continuous coevolutionary process between host and pathogen has resulted in a reservoir of highly diverse R proteins in plants, enabling them to counteract a wide range of pathogens and pests.The most common class of R proteins consists of nucleotide-binding (NB)-leucine-rich repeat (LRR) proteins with a tripartite domain architecture, which roughly corresponds to an N-terminal response domain (a coiled coil [CC] or Toll/Interleukin-1 receptor [TIR] domain) involved in downstream signaling, a central molecula...

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HADDOCK versus HADDOCK: New features and performance of HADDOCK2.0 on the CAPRI targets

Cited by 530 publications

References 42 publications

CXCL1/MGSA Is a Novel Glycosaminoglycan (GAG)-binding Chemokine

CXCL1/MGSA Is a Novel Glycosaminoglycan (GAG)-binding Chemokine

Insight into cyanobacterial circadian timing from structural details of the KaiB–KaiC interaction

Structural Determinants at the Interface of the ARC2 and Leucine-Rich Repeat Domains Control the Activation of the Plant Immune Receptors Rx1 and Gpa2

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