PT  - JOURNAL ARTICLE
AU  - Benavente, Juan L
AU  - Siliqi, Dritan
AU  - Infantes, Lourdes
AU  - Lagartera, Laura
AU  - Mills, Alberto
AU  - Gago, Federico
AU  - Ruiz-López, Noemí
AU  - Botella, Miguel A
AU  - Sánchez-Barrena, María J
AU  - Albert, Armando
TI  - The structure and flexibility analysis of the <em>Arabidopsis</em> synaptotagmin 1 reveal the basis of its regulation at membrane contact sites
AID  - 10.26508/lsa.202101152
DP  - 2021 Oct 01
TA  - Life Science Alliance
PG  - e202101152
VI  - 4
IP  - 10
4099  - http://www.life-science-alliance.org/content/4/10/e202101152.short
4100  - http://www.life-science-alliance.org/content/4/10/e202101152.full
SO  - Life Sci. Alliance2021 Oct 01; 4
AB  - Non-vesicular lipid transfer at ER and plasma membrane (PM) contact sites (CS) is crucial for the maintenance of membrane lipid homeostasis. Extended synaptotagmins (E-Syts) play a central role in this process as they act as molecular tethers of ER and PM and as lipid transfer proteins between these organelles. E-Syts are proteins constitutively anchored to the ER through an N-terminal hydrophobic segment and bind the PM via a variable number of C-terminal C2 domains. Synaptotagmins (SYTs) are the plant orthologous of E-Syts and regulate the ER–PM communication in response to abiotic stress. Combining different structural and biochemical techniques, we demonstrate that the binding of SYT1 to lipids occurs through a Ca2+-dependent lipid-binding site and by a site for phosphorylated forms of phosphatidylinositol, thus integrating two different molecular signals in response to stress. In addition, we show that SYT1 displays three highly flexible hinge points that provide conformational freedom to facilitate lipid extraction, protein loading, and subsequent transfer between PM and ER.