SNAREs, tethers and SM proteins: how to overcome the final barriers to membrane fusion?

Membranes need to be brought into direct contact, which requires the removal of the hydration shells of the outer leaflets

Herre Jelger Risselada; Andreas Mayer

2020

Scholarcy highlights

  • Membranes need to be brought into direct contact, which requires the removal of the hydration shells of the outer leaflets
  • It is energetically feasible to drive this apposition through the mechanical force that is exerted by fusion proteins — at least for inducing point-like contacts
  • In addition, we take into account the association of SNARE complexes with tether/SM proteins, which themselves are fixed between the membranes in the contact zone, it is conceivable that a movement of the SNARE C-termini out of the pore might be obstructed
  • Its curvature is directly determined by the apparent contact angle between the adhering vesicles, i.e. by the relative size of the docking zone. This principle might provide an explanation of why attachment of voluminous proteins to SNARE complexes can push a fusion reaction from arrested hemifusion all the way up to complete expansion of the fusion pore, as observed through the fusion of yeast vacuoles in vitro and in vivo
  • These considerations provide examples supporting the notion that the steric effects of fusion proteins and the geometric properties of the docking and fusion zone have an important impact on the energetics of the fusion process, which must be taken into account
  • The presence of these voluminous complexes can raise the interfacial free energy of the vertex by putting SNAREs into a ‘higher gear’, increasing the contact angle between the vacuoles and imposing a direct steric effect on the membranes

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