Rearrangements under confinement lead to increased binding energy of Synaptotagmin‐1 with anionic membranes in Mg2+ and Ca2+. Issue 9 (10th April 2018)

• Record Type: Journal Article
• Authors: Gruget, Clémence; Coleman, Jeff; Bello, Oscar; Krishnakumar, Shyam S.; Perez, Eric; Rothman, James E.; Pincet, Frederic; Donaldson, Stephen H.
• Is Part Of: FEBS letters. Volume 592:Issue 9(2018)
• Page Start: 1497
• Page End: 1506
• Publication Date: 2018-04-10
• Subjects: membrane fusion -- neurotransmission -- synaptotagmin; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13040
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Synaptotagmin‐1 (Syt1) is the primary calcium sensor (Ca 2+ ) that mediates neurotransmitter release at the synapse. The tandem C2 domains (C2A and C2B) of Syt1 exhibit functionally critical, Ca 2+ ‐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 k B T in EGTA, ~10 k B T in Mg 2+ and ~18 k B T in Ca 2+ . Molecular rearrangements measured during confinement are more prevalent in Ca 2+ and Mg 2+ 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 Ca 2+ ‐activation process in synaptic transmission. Abstract :