PDBsum entry 5kp9

Structural protein

PDB id: 5kp9

Contents

Protein chain

202 a.a.

PDB id:

5kp9

Name:

Structural protein

Title:

Structure of nanoparticle released from enveloped protein nanoparticle

Structure:

Epn-01 . Chain: b. Synonym: enveloped protein nanoparticle. Engineered: yes

Source:

Thermotoga maritima, human immunodeficiency virus type 1 group m subtype b (isolate bh10). HIV-1. Organism_taxid: 2336, 11678. Strain: isolate bh10. Gene: tm_0066, gag. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t

Authors:

J.Votteler,C.Ogohara,S.Yi,Y.Hsia,U.Natterman,D.M.Belnap,N.P.King, W.I.Sundquist

Key ref:

J.Votteler et al. (2016). Designed proteins induce the formation of nanocage-containing extracellular vesicles. Nature, 540, 292-295. PubMed id: 27919066

Date:

02-Jul-16 Release date: 07-Dec-16

Protein chain

P03347  (GAG_HV1B1) -  Gag polyprotein from Human immunodeficiency virus type 1 group M subtype B (isolate BH10)

Seq: 512 a.a.

Struc: 202 a.a.*

Protein chain

Q9WXS1  (Q9WXS1_THEMA) -  2-dehydro-3-deoxyphosphogluconate aldolase/4-hydroxy-2-oxoglutarate aldolase from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)

Seq: 205 a.a.

Struc: 202 a.a.*

* PDB and UniProt seqs differ at 149 residue positions (black crosses)

Nature 540:292-295 (2016)

PubMed id: 27919066

Designed proteins induce the formation of nanocage-containing extracellular vesicles.

J.Votteler, C.Ogohara, S.Yi, Y.Hsia, U.Nattermann, D.M.Belnap, N.P.King, W.I.Sundquist.

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.