Mechanism of negative membrane curvature generation by the IRSP53 I-BAR domain

摘要: Abstract The membrane sculpting ability of BAR domains has been attributed to the intrinsic curvature their banana-shaped dimeric structure. However, there is often a mismatch between this and diameter tubules generated. For example, I-BAR are almost flat but generate much higher curvature. Furthermore, F-BAR quite similar, former generates positive latter negative Here, we use implicit-solvent computer modeling show that bending IRSP53 domain dictated by its oligomeric structure, whose completely unrelated dimer. We find dimers undergo lateral end-to-end interactions form oligomers. interactions, which can occur with varying register, stronger give curved shape binding interface on convex surface. Two other I-BARs (MIM I-BARa) gave similar results, whereas sheet make concave, consistent generation. Individual orient parallel tube axis when radius small, perpendicular orientation preferred for larger tubes. This orientational preference exists even in form. Helical spirals interiors stable at density comparable experimental measurements. sorting ratio computed from our energies also Significance Statement Changes required numerous biological processes, such as endocytosis/exocytosis, viral budding, filopodia formation, etc. one protein family mediates these changes, mechanism action not entirely clear. possess an does match membranes generated.This especially true known well-studied forms oligomers individual matches curvatures resolves long-standing mystery about