Discrimination between biological interfaces and crystal-packing contacts

Tsuchiya, Yuko

doi:10.2147/aabc.s4255

Cited by 24 publications

(27 citation statements)

References 52 publications

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“…9, A and B). Each monomer-monomer interface has approximately 60 amino acids and a total of 964 Å 2 of buried surface area, which is a reasonable value based on previously reported studies analyzing interfaces in protein complexes (Tsuchiya et al, 2008;Krissinel and Henrick, 2007). Interestingly, a similar arrangement of the CSR regions was reported for the OsCESA8CatD dimer (Olek et al, 2014).…”

Section: Computational Modeling Of Atcesa1catd Trimerssupporting

confidence: 82%

“…Each monomer-monomer interface has approximately 32 amino acid residues and a total of 750 Å 2 of buried surface area. This value is lower than that obtained for AtCESA1CatD-m1, but is a reasonable value for a stable protein-protein interface (Tsuchiya et al, 2008;Krissinel and Henrick, 2007). The Figure 5.…”

Section: Computational Modeling Of Atcesa1catd Trimersmentioning

confidence: 54%

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A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers

et al. 2015

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A cellulose synthesis complex with a "rosette" shape is responsible for synthesis of cellulose chains and their assembly into microfibrils within the cell walls of land plants and their charophyte algal progenitors. The number of cellulose synthase proteins in this large multisubunit transmembrane protein complex and the number of cellulose chains in a microfibril have been debated for many years. This work reports a low resolution structure of the catalytic domain of CESA1 from Arabidopsis (Arabidopsis thaliana; AtCESA1CatD) determined by small-angle scattering techniques and provides the first experimental evidence for the self-assembly of CESA into a stable trimer in solution. The catalytic domain was overexpressed in Escherichia coli, and using a two-step procedure, it was possible to isolate monomeric and trimeric forms of AtCESA1CatD. The conformation of monomeric and trimeric AtCESA1CatD proteins were studied using small-angle neutron scattering and small-angle x-ray scattering. A series of AtCESA1CatD trimer computational models were compared with the small-angle x-ray scattering trimer profile to explore the possible arrangement of the monomers in the trimers. Several candidate trimers were identified with monomers oriented such that the newly synthesized cellulose chains project toward the cell membrane. In these models, the class-specific region is found at the periphery of the complex, and the plant-conserved region forms the base of the trimer. This study strongly supports the "hexamer of trimers" model for the rosette cellulose synthesis complex that synthesizes an 18-chain cellulose microfibril as its fundamental product.

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Section: Computational Modeling Of Atcesa1catd Trimerssupporting

confidence: 82%

Section: Computational Modeling Of Atcesa1catd Trimersmentioning

confidence: 54%

A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers

et al. 2015

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“…However, for 41 homodimers in the dataset, as they were composed of more than two subunits, that is, a multimer of homodimers, we chose the dimers with the largest interface area. For another nine homodimers, we gave preference to crystal‐packing contacts of two subunits in the adjacent unit cells over the contact of two subunits within the asymmetric unit, because the authors in the primary citation of the PDB data indicate it (1ex2, 1h6p, 1l6r, and 2okg) or because the crystal‐packing contact has the largest contact area and is judged as the most probable biologically relevant dimer interface in the crystal by the discrimination method between biological interfaces and crystal contacts developed by Tsuchiya et al 27. (1xma, 1xvh, 2be3, 2cu3, and 2p7j).…”

Section: Methodsmentioning

confidence: 99%

Dynamic features of homodimer interfaces calculated by normal‐mode analysis

et al. 2012

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Knowledge of the dynamic features of protein interfaces is necessary for a deeper understanding of protein-protein interactions. We performed normal-mode analysis (NMA) of 517 nonredundant homodimers and their protomers to characterize dimer interfaces from a dynamic perspective. The motion vector calculated by NMA for each atom of a dimer was decomposed into internal and external motion vectors in individual component subunits, followed by the averaging of time-averaged correlations between these vectors over atom pairs in the interface. This averaged correlation coefficient (ACC) was defined for various combinations of vectors and investigated in detail. ACCs decrease exponentially with an increasing interface area and r-value, that is, interface area divided by the entire subunit surface area. As the r-value reflects the nature of dimer formation, the result suggests that both the interface area and the nature of dimer formation are responsible for the dynamic properties of dimer interfaces. For interfaces with small or medium r-values and without intersubunit entanglements, ACCs are found to increase on dimer formation when compared with those in the protomer state. In contrast, ACCs do not increase on dimer formation for interfaces with large r-values and intersubunit entanglements such as in interwinding dimers. Furthermore, relationships between ACCs for intrasubunit atom pairs and for intersubunit atom pairs are found to significantly differ between interwinding and noninterwinding dimers for external motions. External motions are considered as an important factor for characterizing dimer interfaces.

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“…We thus chose to start our interrogation of JH2-mediated regulation of JAK2 kinase activity from modeling the JH1–JH2 complex. As both JH1 and JH2 adopt a kinase fold, one practical strategy is to model the JH1–JH2 complex using dimeric kinase forms indicated by crystal structures of kinase complexes or by assembly derived from crystal packing [14]. For EGFR [15] and PKR [16], [17], the dimeric unit implicated by crystal packing helped to reveal novel dimerization and activation mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Ab Initio Modeling and Experimental Assessment of Janus Kinase 2 (JAK2) Kinase-Pseudokinase Complex Structure

Wan

McClendon

et al. 2013

PLoS Comput Biol

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The Janus Kinase 2 (JAK2) plays essential roles in transmitting signals from multiple cytokine receptors, and constitutive activation of JAK2 results in hematopoietic disorders and oncogenesis. JAK2 kinase activity is negatively regulated by its pseudokinase domain (JH2), where the gain-of-function mutation V617F that causes myeloproliferative neoplasms resides. In the absence of a crystal structure of full-length JAK2, how JH2 inhibits the kinase domain (JH1), and how V617F hyperactivates JAK2 remain elusive. We modeled the JAK2 JH1–JH2 complex structure using a novel informatics-guided protein-protein docking strategy. A detailed JAK2 JH2-mediated auto-inhibition mechanism is proposed, where JH2 traps the activation loop of JH1 in an inactive conformation and blocks the movement of kinase αC helix through critical hydrophobic contacts and extensive electrostatic interactions. These stabilizing interactions are less favorable in JAK2-V617F. Notably, several predicted binding interfacial residues in JH2 were confirmed to hyperactivate JAK2 kinase activity in site-directed mutagenesis and BaF3/EpoR cell transformation studies. Although there may exist other JH2-mediated mechanisms to control JH1, our JH1–JH2 structural model represents a verifiable working hypothesis for further experimental studies to elucidate the role of JH2 in regulating JAK2 in both normal and pathological settings.

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Discrimination between biological interfaces and crystal-packing contacts

Cited by 24 publications

References 52 publications

A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers

A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers

Dynamic features of homodimer interfaces calculated by normal‐mode analysis

Ab Initio Modeling and Experimental Assessment of Janus Kinase 2 (JAK2) Kinase-Pseudokinase Complex Structure

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