TY - JOUR T1 - The structure and flexibility analysis of the <em>Arabidopsis</em> synaptotagmin 1 reveal the basis of its regulation at membrane contact sites JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101152 VL - 4 IS - 10 SP - e202101152 AU - Juan L Benavente AU - Dritan Siliqi AU - Lourdes Infantes AU - Laura Lagartera AU - Alberto Mills AU - Federico Gago AU - Noemí Ruiz-López AU - Miguel A Botella AU - María J Sánchez-Barrena AU - Armando Albert Y1 - 2021/10/01 UR - https://www.life-science-alliance.org/content/4/10/e202101152.abstract N2 - 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. ER -