Molecular Insights into Distinct Membrane-insertion Behaviors and Mechanisms of 20 Amino Acids:an All-atom MD Simulation Study

Interfacial interactions of proteins with cell membranes play important roles in fundamental physiological processes of cells.The binding of proteins to membranes involves interactions between amino acids and membranes.However,the mechanism underlying amino acids'membrane behavior remains elusive.Herein,all-atom molecular dynamic simulations were applied to comprehensively investigating the molecular details of interactions between 20 amino acids with DOPC membranes.Our results show that 20 amino acids exhibit distinct membrane insertion activities,which are not simply determined by the side chain properties of amino acids.Aromatic Tyr/Phe/Trp,hydrophobic Val/Ile/Leu/Met,positively-charged Arg and hydrophilic Cys exhibit significantly strong membrane insertion capacities with different characteristic insertion depths and insertion angles.Surprisingly,hydrophobic Ala,positively-charged His/Lys,hydrophilic Asn/Ser/Gln/Thr,negatively-charged Asp/Glu and Pro/Gly have low membrane insertion capabilities.Considering the chemical structures and interaction details of amino acids with membranes,we suggest that the abundance and diversity of interaction sites and types,the synergistic effect of hydrophilic and hydrophobic interactions of amino acids with membranes and the structural flexibility of amino acids are key factors for determining membrane insertion capabilities and characteristics of amino acids.Our study sheds light on the atomic mechanism of interactions between single amino acids and membranes.

Interaction of SynaptotagminⅠ with Phospholipid Membrane: A Monolayer Study

Synaptotagmin Ⅰ(sytⅠ) is an abundant integral membrane protein of the synaptic vesicle and the C2A domain is an important functional domain in the cytoplasmic part of sytⅠ. C2A prefers to interact with plasmic membranes of neuron cells in vivo and such interaction is closely related to the sytⅠ physiological function as a Ca 2+ sensor in the Ca 2+ regulated neurotransmitter release. However, the interaction nature between C2A and phospholipids is not well understood. Monolayers at an air/water interface were used to study the interaction between C2A and a phospholipid membrane. The results show that C2A preferentially inserts into the negatively charged phosphatidylserine monolayer and Ca 2+ ions are required for the interaction. Electrostatic force is mostly responsible for the insertion of C2A into dipalmitoyl phosphatidylserine monolayers.

Alb4 of Arabidopsis Promotes Assembly and Stabilization of a Non Chlorophyll-Binding Photosynthetic Complex, the CF1CF0-ATP Synthase

All members of the YidC/Oxal/Alb3 protein family are evolutionarily conserved and appear to function in membrane protein integration and protein complex stabilization. Here, we report on a second thylakoidal isoform of Alb3, named Alb4. Analysis of Arabidopsis knockout mutant lines shows that AIb4 is required in assembly and/or stability of the CF1CF0-ATP synthase （ATPase）. alb4 mutant lines not only have reduced steady-state levels of ATPase subunits, but also their assembly into high-molecular-mass complexes is altered, leading to a reduction of ATP synthesis in the mutants. Moreover, we show that Alb4 but not AIb3 physically interacts with the subunits CF1β and CF0ll. Summarizing, the data indicate that AIb4 functions to stabilize or promote assembly of CF1 during its attachment to the membrane-embedded CF0 part.