Tip-to-tip interaction in the crystal packing of PACSIN 2 is important in regulating tubulation activity

The F-BAR domain containing proteins PACSINs are cytoplasmic phosphoproteins involved in various mem-brane deformations,such as actin reorganization,vesicle transport and microtubule movement.Our previous study shows that all PACSINs are composed of crescent shaped dimers with two wedge loops,and the wedge loop-mediated lateral interaction between neighboring dimers is important for protein packing and tubulation activity.Here,from the crystal packing of PACSIN 2,we observed a tight tip-to-tip interaction,in addition to the wedge loop-mediated lateral interaction.With this tip-to-tip interaction,the whole packing of PACSIN 2 shows a spiral-like assem-bly with a central hole from the top view.Elimination of this tip-to-tip connection inhibited the tubulation function of PACSIN 2,indicating that tip-to-tip interaction plays an important role in membrane deformation activity.Together with our previous study,we proposed a packing model for the assembly of PACSIN 2 on membrane,where the pro-teins are connected by tip-to-tip and wedge loop-mediated lateral interactions on the surface of membrane to gener-ate various diameter tubules.