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The Neck Region of the C-type Lectin DC-SIGN Regulates Its Surface Spatiotemporal Organization and Virus-binding Capacity on Antigen-presenting Cells

Manzo, Carlo ; Torreno-Pina, Juan A. ; Joosten, Ben ; Reinieren-Beeren, Inge ; Gualda, Emilio J. ; Loza-Alvarez, Pablo ; Figdor, Carl G. ; Garcia-Parajo, Maria F. ; Cambi, Alessandra

The Journal of biological chemistry, 2012-11, Vol.287 (46), p.38946-38955 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
The Neck Region of the C-type Lectin DC-SIGN Regulates Its Surface Spatiotemporal Organization and Virus-binding Capacity on Antigen-presenting Cells
Autor: Manzo, Carlo ; Torreno-Pina, Juan A. ; Joosten, Ben ; Reinieren-Beeren, Inge ; Gualda, Emilio J. ; Loza-Alvarez, Pablo ; Figdor, Carl G. ; Garcia-Parajo, Maria F. ; Cambi, Alessandra
Assuntos: Animals ; Antigen-Presenting Cells - metabolism ; Binding Sites ; Biophysics - methods ; C-type Lectins ; Cell Adhesion Molecules - metabolism ; Cell Membrane - metabolism ; CHO Cells ; Clathrin - metabolism ; Cricetinae ; Cricetulus ; Cytoplasm - metabolism ; Dendritic Cells ; Dendritic Cells - cytology ; Diffusion ; Humans ; Lectins - chemistry ; Lectins, C-Type - metabolism ; Membrane Biology ; Membrane Biophysics ; Membrane Nanodomains ; Mice ; Microscopic Imaging ; Models, Biological ; NIH 3T3 Cells ; Protein Binding ; Receptor Dynamics ; Receptor Structure-Function ; Receptors, Cell Surface - metabolism ; Surface Properties ; Time Factors ; Virus Entry
É parte de: The Journal of biological chemistry, 2012-11, Vol.287 (46), p.38946-38955
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Both authors contributed equally to this work.
Descrição: The C-type lectin DC-SIGN expressed on dendritic cells (DCs) facilitates capture and internalization of a plethora of different pathogens. Although it is known that DC-SIGN organizes in nanoclusters at the surface of DCs, the molecular mechanisms responsible for this well defined nanopatterning and role in viral binding remain enigmatic. By combining biochemical and advanced biophysical techniques, including optical superresolution and single particle tracking, we demonstrate that DC-SIGN intrinsic nanoclustering strictly depends on its molecular structure. DC-SIGN nanoclusters exhibited free, Brownian diffusion on the cell membrane. Truncation of the extracellular neck region, known to abrogate tetramerization, significantly reduced nanoclustering and concomitantly increased lateral diffusion. Importantly, DC-SIGN nanocluster dissolution exclusively compromised binding to nanoscale size pathogens. Monte Carlo simulations revealed that heterogeneity on nanocluster density and spatial distribution confers broader binding capabilities to DC-SIGN. As such, our results underscore a direct relationship between spatial nanopatterning, driven by intermolecular interactions between the neck regions, and receptor diffusion to provide DC-SIGN with the exquisite ability to dock pathogens at the virus length scale. Insight into how virus receptors are organized prior to virus binding and how they assemble into functional platforms for virus docking is helpful to develop novel strategies to prevent virus entry and infection. Background: Nanoclusters of the C-type lectin DC-SIGN on dendritic cells act as docking sites for viral binding. Results: The extracellular neck region is responsible for nanocluster formation and necessary for virus binding. Conclusion: Heterogeneous nanocluster density and spatial distribution confer broad binding capabilities to DC-SIGN. Significance: Insights into how virus receptors preorganize and assemble into docking platforms contribute to clarifying mechanisms of virus entry.
Editor: United States: Elsevier Inc
Idioma: Inglês

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The Neck Region of the C-type Lectin DC-SIGN Regulates Its Surface Spatiotemporal Organization and Virus-binding Capacity on Antigen-presenting Cells

Manzo, Carlo ; Torreno-Pina, Juan A. ; Joosten, Ben ; Reinieren-Beeren, Inge ; Gualda, Emilio J. ; Loza-Alvarez, Pablo ; Figdor, Carl G. ; Garcia-Parajo, Maria F. ; Cambi, Alessandra

United States: Elsevier Inc

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