Details

Autor(en) / Beteiligte

• Leung, Carl
• Hodel, Adrian W.
• Brennan, Amelia J.
• Lukoyanova, Natalya
• Tran, Sharon
• House, Colin M.
• Kondos, Stephanie C.
• Whisstock, James C.
• Dunstone, Michelle A.
• Trapani, Joseph A.
• Voskoboinik, Ilia
• Saibil, Helen R.
• Hoogenboom, Bart W.

Titel

Real-time visualization of perforin nanopore assembly

Ist Teil von

• Nature nanotechnology, 2017-05, Vol.12 (5), p.467-473

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Perforin is a key protein of the vertebrate immune system. Secreted by cytotoxic lymphocytes as soluble monomers, perforin can self-assemble into oligomeric pores of 10–20 nm inner diameter in the membranes of virus-infected and cancerous cells. These large pores facilitate the entry of pro-apoptotic granzymes, thereby rapidly killing the target cell. To elucidate the pathways of perforin pore assembly, we carried out real-time atomic force microscopy and electron microscopy studies. Our experiments reveal that the pore assembly proceeds via a membrane-bound prepore intermediate state, typically consisting of up to approximately eight loosely but irreversibly assembled monomeric subunits. These short oligomers convert to more closely packed membrane nanopore assemblies, which can subsequently recruit additional prepore oligomers to grow the pore size. Perforin monomers self-assemble into pre-pores that first insert into the membrane and then recruit additional subunits to grow in size.