 |
PDBsum entry 5kp9
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Structural protein
|
PDB id
|
|
|
|
5kp9
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Designed proteins induce the formation of nanocage-Containing extracellular vesicles.
|
|
|
Authors
|
|
J.Votteler,
C.Ogohara,
S.Yi,
Y.Hsia,
U.Nattermann,
D.M.Belnap,
N.P.King,
W.I.Sundquist.
|
|
|
Ref.
|
|
Nature, 2016,
540,
292-295.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Complex biological processes are often performed by self-organizing
nanostructures comprising multiple classes of macromolecules, such as ribosomes
(proteins and RNA) or enveloped viruses (proteins, nucleic acids and lipids).
Approaches have been developed for designing self-assembling structures
consisting of either nucleic acids or proteins, but strategies for engineering
hybrid biological materials are only beginning to emerge. Here we describe the
design of self-assembling protein nanocages that direct their own release from
human cells inside small vesicles in a manner that resembles some viruses. We
refer to these hybrid biomaterials as 'enveloped protein nanocages' (EPNs).
Robust EPN biogenesis requires protein sequence elements that encode three
distinct functions: membrane binding, self-assembly, and recruitment of the
endosomal sorting complexes required for transport (ESCRT) machinery. A variety
of synthetic proteins with these functional elements induce EPN biogenesis,
highlighting the modularity and generality of the design strategy. Biochemical
analyses and cryo-electron microscopy reveal that one design, EPN-01, comprises
small (~100 nm) vesicles containing multiple protein nanocages that closely
match the structure of the designed 60-subunit self-assembling scaffold. EPNs
that incorporate the vesicular stomatitis viral glycoprotein can fuse with
target cells and deliver their contents, thereby transferring cargoes from one
cell to another. These results show how proteins can be programmed to direct the
formation of hybrid biological materials that perform complex tasks, and
establish EPNs as a class of designed, modular, genetically-encoded
nanomaterials that can transfer molecules between cells.
|
|
|
|
|
|
|
