Unknown

Dataset Information

0

Structural characterization of the Rabphilin-3A-SNAP25 interaction.


ABSTRACT: Membrane fusion is essential in a myriad of eukaryotic cell biological processes, including the synaptic transmission. Rabphilin-3A is a membrane trafficking protein involved in the calcium-dependent regulation of secretory vesicle exocytosis in neurons and neuroendocrine cells, but the underlying mechanism remains poorly understood. Here, we report the crystal structures and biochemical analyses of Rabphilin-3A C2B-SNAP25 and C2B-phosphatidylinositol 4,5-bisphosphate (PIP2) complexes, revealing how Rabphilin-3A C2 domains operate in cooperation with PIP2/Ca2+ and SNAP25 to bind the plasma membrane, adopting a conformation compatible to interact with the complete SNARE complex. Comparisons with the synaptotagmin1-SNARE show that both proteins contact the same SNAP25 surface, but Rabphilin-3A uses a unique structural element. Data obtained here suggest a model to explain the Ca2+-dependent fusion process by membrane bending with a myriad of variations depending on the properties of the C2 domain-bearing protein, shedding light to understand the fine-tuning control of the different vesicle fusion events.

SUBMITTER: Ferrer-Orta C 

PROVIDER: S-EPMC5502619 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structural characterization of the Rabphilin-3A-SNAP25 interaction.

Ferrer-Orta Cristina C   Pérez-Sánchez María Dolores MD   Coronado-Parra Teresa T   Silva Cristina C   López-Martínez David D   Baltanás-Copado Jesús J   Gómez-Fernández Juan Carmelo JC   Corbalán-García Senena S   Verdaguer Núria N  

Proceedings of the National Academy of Sciences of the United States of America 20170620 27


Membrane fusion is essential in a myriad of eukaryotic cell biological processes, including the synaptic transmission. Rabphilin-3A is a membrane trafficking protein involved in the calcium-dependent regulation of secretory vesicle exocytosis in neurons and neuroendocrine cells, but the underlying mechanism remains poorly understood. Here, we report the crystal structures and biochemical analyses of Rabphilin-3A C2B-SNAP25 and C2B-phosphatidylinositol 4,5-bisphosphate (PIP<sub>2</sub>) complexes  ...[more]

Similar Datasets

| S-EPMC4703873 | biostudies-literature
| S-EPMC2386734 | biostudies-literature
| S-EPMC7862399 | biostudies-literature
| S-EPMC9873702 | biostudies-literature
| S-EPMC11319786 | biostudies-literature
| S-EPMC2222762 | biostudies-other
| S-EPMC3870689 | biostudies-literature
| S-EPMC1868247 | biostudies-literature
| S-EPMC2133937 | biostudies-other
| S-EPMC10786657 | biostudies-literature