Structure Collisions between Interacting Proteins

Emig, Dorothea; Sander, Oliver; Mayr, Gabriele; Albrecht, Mario

doi:10.1371/journal.pone.0019581

Cited by 3 publications

(4 citation statements)

References 33 publications

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“…The rotation angle between EC1 (chain A) and EC1 (chain B) in the strand-swap dimer was calculated with DynDom45. Overlapping volumes were evaluated with MSMS of the CHIMERA suite4647.…”

Section: Methodsmentioning

confidence: 99%

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Disruption of cell adhesion by an antibody targeting the cell-adhesive intermediate (X-dimer) of human P-cadherin

Kudo

Caaveiro

Nagatoishi

et al. 2017

Sci Rep

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Human P-cadherin is a cell adhesion protein of the family of classical cadherins, the overexpression of which is correlated with poor prognosis in various types of cancer. Antibodies inhibiting cell-cell adhesion mediated by P-cadherin show clear therapeutic effect, although the mechanistic basis explaining their effectiveness is still unclear. Based on structural, physicochemical, and functional analyses, we have elucidated the molecular mechanism of disruption of cell adhesion by antibodies targeting human P-cadherin. Herein we have studied three different antibodies, TSP5, TSP7, and TSP11, each recognizing a different epitope on the surface of the cell-adhesive domain (EC1). Although all these three antibodies recognized human P-cadherin with high affinity, only TSP7 disrupted cell adhesion. Notably, we demonstrated that TSP7 abolishes cell adhesion by disabling the so-called X-dimer (a kinetic adhesive intermediate), in addition to disrupting the strand-swap dimer (the final thermodynamic state). The inhibition of the X-dimer was crucial for the overall inhibitory effect, raising the therapeutic value of a kinetic intermediary not only for preventing, but also for reversing, cell adhesion mediated by a member of the classical cadherin family. These findings should help to design more innovative and effective therapeutic solutions targeting human P-cadherin.

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“…The rotation angle between EC1 (chain A) and EC1 (chain B) in the strand-swap dimer was calculated with DynDom45. Overlapping volumes were evaluated with MSMS of the CHIMERA suite4647.…”

Section: Methodsmentioning

confidence: 99%

“…The region where two molecules of TSP7 clash with each other when P-cadherin adopts the X-dimer conformation is highlighted with a dotted line. The overlapping volume was calculated with MSMS46. (e) Binding isotherm of P-cadherin constructs (EC12 K14E, MEC12, or MEC12 K14E) to TSP7.…”

Section: Figurementioning

confidence: 99%

Disruption of cell adhesion by an antibody targeting the cell-adhesive intermediate (X-dimer) of human P-cadherin

Kudo

Caaveiro

Nagatoishi

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…It has been found that separate binding interfaces might not imply simultaneously possible protein interactions [27]. For a given host protein, two binding partners might collide in 3-D space although their binding sites are not overlapping.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Genomic Features With Dynamic Modularity in the Yeast Interactome: A View From the Structural Perspective

Wang

Zheng

2012

IEEE Trans.on Nanobioscience

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The idea of the existence of date and party hubs in protein-protein interaction networks has been debated since it was proposed in 2004. Based on the incorporation of the information extracted from known three-dimensional structures of protein interactions, we revisited the properties associated with date and party hubs previously identified. The correlation of genomic essentiality, gene coexpression, and functional semantic similarity with date and party hubs were examined. The number of interaction interfaces associated with each hub was taken into account. The results suggested that the identification of date and party hubs based on their network connectivity and expression profiles with interaction partners may be incomplete. The number of interaction interfaces could play an important role in examining functional and topological properties associated with each hub protein. The observation is robust to the choice of degree cutoffs for hubs. Furthermore, we found that while singlish-interface hubs seem to correspond mostly to date hub, it appears that there is no significant difference between the proportions of multi-interface proteins categorized as date and as party hubs.

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“…It has been suggested that separate binding interfaces might not imply Table 5 The impact of the selection of the threshold of defining hubs with multi interfaces simultaneously possible protein interactions [19]. For a given host protein, two binding partners might collide in 3D space although their binding sits are not overlapping.…”

Section: Discussionmentioning

confidence: 99%

Correlation of genomics features with the date and party hub distinction: A view from three dimensional protein structures

Wang

Zheng

2011

2011 IEEE International Conference on Bioinformatics and Biomedicine Workshops (BIBMW)

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The idea of the existence of date and party hubs in protein-protein interaction networks (PPI) has been influential since it was proposed in 2004. However, the validity of such a distinction remains a subject of debate. Based on the incorporation of the information extracted from known three-dimensional structures of protein interactions, we revisited the properties associated with date and party hubs previously identified. The correlation of genomic essentiality and gene coexpression with the date and party hubs were studied. The results suggested that the identification of date and party hubs based on their network connectivity and expression profiles with interaction partners may be incomplete. The number of interaction interfaces could play an important role in examining the topological properties associate with each protein included in PPI networks.

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Structure Collisions between Interacting Proteins

Cited by 3 publications

References 33 publications

Disruption of cell adhesion by an antibody targeting the cell-adhesive intermediate (X-dimer) of human P-cadherin

Disruption of cell adhesion by an antibody targeting the cell-adhesive intermediate (X-dimer) of human P-cadherin

Correlation of Genomic Features With Dynamic Modularity in the Yeast Interactome: A View From the Structural Perspective

Correlation of genomics features with the date and party hub distinction: A view from three dimensional protein structures

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