INVESTIGADORES
BELLO oscar daniel
artículos
Título:
Rearrangements under confinement lead to increased binding energy of Synaptotagmin-1 with anionic membranes in Mg 2+ and Ca 2+
Autor/es:
GRUGET, CLÉMENCE; COLEMAN, JEFF; BELLO, OSCAR; KRISHNAKUMAR, SHYAM S.; PEREZ, ERIC; ROTHMAN, JAMES E.; PINCET, FREDERIC; DONALDSON, STEPHEN H.
Revista:
FEBS LETTERS
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Año: 2018
ISSN:
0014-5793
Resumen:
Synaptotagmin-1 (Syt1) is the primary calcium sensor (Ca2+ ) that mediates neurotransmitter release at the synapse. The tandem C2 domains (C2A and C2B) of Syt1 exhibit functionally critical, Ca2+ -dependent interactions with the plasma membrane. With the surface forces apparatus, we directly measure the binding energy of membrane-anchored Syt1 to an anionic membrane and find that Syt1 binds with ~6 kB T in EGTA, ~10 kB T in Mg2+ and ~18 kB T in Ca2+ . Molecular rearrangements measured during confinement are more prevalent in Ca2+ and Mg2+ and suggest that Syt1 initially binds through C2B, then reorients the C2 domains into the preferred binding configuration. These results provide energetic and mechanistic details of the Syt1 Ca2+ -activation process in synaptic transmission.
