A0A2P1JNM1 · A0A2P1JNM1_LASV
- ProteinPre-glycoprotein polyprotein GP complex
- GeneGPC
- StatusUniProtKB unreviewed (TrEMBL)
- Organism
- Amino acids490 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
Function
function
Glycoprotein G1
Forms the virion spikes together with glycoprotein G2. The glycoprotein spike trimers are connected to the underlying matrix. Interacts with the host receptor. Mediates virus attachment to the host primary receptor alpha-dystroglycan DAG1 (alpha-DG) at the cell surface. This attachment induces virion internalization apparently through macropinocytosis. Following endocytosis, there is a pH-dependent switch from binding DAG1 to the host lysosomal receptor LAMP1. This latter binding triggers the dissociation of GP1, exposing the fusion subunit, GP2, such that fusion can occur. Down-modulates host DAG1.
Glycoprotein G2
Forms the virion spikes together with glycoprotein G1. The glycoprotein spike trimers are connected to the underlying matrix. Class I viral fusion protein that directs fusion of viral and host endosomal membranes, leading to delivery of the nucleocapsid into the cytoplasm. Membrane fusion is mediated by irreversible conformational changes induced by acidification.
Stable signal peptide
Functions as a cleaved signal peptide that is retained as the third component of the GP complex (GP-C). Helps to stabilize the spike complex in its native conformation. The SSP is required for efficient glycoprotein expression, post-translational maturation cleavage of G1 and G2, glycoprotein transport to the cell surface plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 57 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Site | 58-59 | Cleavage; by host signal peptidase | ||||
Sequence: ST | ||||||
Site | 91 | Binding to the host receptor LAMP1 | ||||
Sequence: H | ||||||
Site | 92 | Binding to the host receptor LAMP1 | ||||
Sequence: H | ||||||
Site | 229 | Binding to the host receptor LAMP1 | ||||
Sequence: H | ||||||
Site | 258-259 | Cleavage; by host MBTPS1 | ||||
Sequence: LG | ||||||
Binding site | 454 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 456 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 462 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 466 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 474 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 476 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | host cell endoplasmic reticulum membrane | |
Cellular Component | host cell Golgi membrane | |
Cellular Component | host cell plasma membrane | |
Cellular Component | membrane | |
Cellular Component | viral envelope | |
Cellular Component | virion membrane | |
Molecular Function | metal ion binding | |
Biological Process | fusion of virus membrane with host endosome membrane | |
Biological Process | receptor-mediated endocytosis of virus by host cell | |
Biological Process | virion attachment to host cell |
Keywords
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended namePre-glycoprotein polyprotein GP complex
- Short namesPre-GP-C
- Cleaved into 3 chains
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Negarnaviricota > Polyploviricotina > Ellioviricetes > Bunyavirales > Arenaviridae > Mammarenavirus
- Virus hosts
Accessions
- Primary accessionA0A2P1JNM1
Subcellular Location
UniProt Annotation
GO Annotation
Glycoprotein G2
Virion membrane ; Single-pass membrane protein
Host endoplasmic reticulum membrane ; Single-pass membrane protein
Host Golgi apparatus membrane ; Single-pass membrane protein
Host cell membrane ; Single-pass membrane protein
Note: Binding to the stable signal peptide masks endogenous ER localization signals in the cytoplasmic domain of G2 to ensure that only the fully assembled, tripartite GP complex is transported for virion assembly.
Glycoprotein G1
Virion membrane ; Peripheral membrane protein
Host endoplasmic reticulum membrane ; Peripheral membrane protein
Host Golgi apparatus membrane ; Peripheral membrane protein
Host cell membrane ; Peripheral membrane protein
Stable signal peptide
Virion membrane ; Single-pass type II membrane protein
Host endoplasmic reticulum membrane ; Single-pass type II membrane protein
Host Golgi apparatus membrane ; Single-pass type II membrane protein
Host cell membrane ; Single-pass type II membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 2-17 | Extracellular | ||||
Sequence: GQIITFFQEVPHVIEE | ||||||
Transmembrane | 21-52 | Helical | ||||
Sequence: IVLIALSLLAILKGIYNVATCGLFGLVSFLLL | ||||||
Topological domain | 34-58 | Cytoplasmic | ||||
Sequence: GIYNVATCGLFGLVSFLLLCGRSCS | ||||||
Transmembrane | 427-449 | Helical | ||||
Sequence: LGLVDLFVFSTSFYLISIFLHLV | ||||||
Topological domain | 453-490 | Cytoplasmic | ||||
Sequence: THRHITGKPCPKPHRLNHMGICSCGLYKHPGVPVKWKR |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, lipidation, chain, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed; by host | ||||
Sequence: M | ||||||
Lipidation | 2 | N-myristoyl glycine; by host | ||||
Sequence: G | ||||||
Chain | PRO_5023316434 | 2-58 | Stable signal peptide | |||
Sequence: GQIITFFQEVPHVIEEVMNIVLIALSLLAILKGIYNVATCGLFGLVSFLLLCGRSCS | ||||||
Chain | PRO_5023316435 | 2-490 | Pre-glycoprotein polyprotein GP complex | |||
Sequence: GQIITFFQEVPHVIEEVMNIVLIALSLLAILKGIYNVATCGLFGLVSFLLLCGRSCSTTYKGVYELQTLELDMANLNMTMPLSCTKNNSHHYIMVGNETGLELTLTNTSIINHKFCNLSDAHKKNLYDHALMSIISTFHLSIPNFNQYEAMSCDFNGGKISVQYNLSHTYAVDAANHCGTIANGVLQTFMRMAWGGSYIALDSGKGSWDCIMTSYQYLVIQNTTWEDHCQFSRPSPIGYLGLLSQRTRDIYISRRLLGTFTWTLSDSEGNETPGGYCLTRWMLIEAELKCFGNTAVAKCNEKHDEEFCDMLRLFDFNKQAIRRLKTEAQMSIQLINKAVNALINDQLIMKNHLRDIMGIPYCNYSKYWYLNHTVTGKTSLPRCWLVSNGSYLNETHFSDDIEQQADNMITELLQKEYIDRQGKTPLGLVDLFVFSTSFYLISIFLHLVKIPTHRHITGKPCPKPHRLNHMGICSCGLYKHPGVPVKWKR | ||||||
Glycosylation | 78 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 85↔230 | |||||
Sequence: CTKNNSHHYIMVGNETGLELTLTNTSIINHKFCNLSDAHKKNLYDHALMSIISTFHLSIPNFNQYEAMSCDFNGGKISVQYNLSHTYAVDAANHCGTIANGVLQTFMRMAWGGSYIALDSGKGSWDCIMTSYQYLVIQNTTWEDHC | ||||||
Glycosylation | 88 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 98 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 108 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 117↔154 | |||||
Sequence: CNLSDAHKKNLYDHALMSIISTFHLSIPNFNQYEAMSC | ||||||
Glycosylation | 118 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 166 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 179↔211 | |||||
Sequence: CGTIANGVLQTFMRMAWGGSYIALDSGKGSWDC | ||||||
Glycosylation | 223 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Chain | PRO_5023316436 | 259-490 | Glycoprotein G2 | |||
Sequence: GTFTWTLSDSEGNETPGGYCLTRWMLIEAELKCFGNTAVAKCNEKHDEEFCDMLRLFDFNKQAIRRLKTEAQMSIQLINKAVNALINDQLIMKNHLRDIMGIPYCNYSKYWYLNHTVTGKTSLPRCWLVSNGSYLNETHFSDDIEQQADNMITELLQKEYIDRQGKTPLGLVDLFVFSTSFYLISIFLHLVKIPTHRHITGKPCPKPHRLNHMGICSCGLYKHPGVPVKWKR | ||||||
Disulfide bond | 278↔291 | |||||
Sequence: CLTRWMLIEAELKC | ||||||
Disulfide bond | 300↔309 | |||||
Sequence: CNEKHDEEFC | ||||||
Disulfide bond | 363↔384 | |||||
Sequence: CNYSKYWYLNHTVTGKTSLPRC | ||||||
Glycosylation | 364 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 372 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 389 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 394 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N |
Post-translational modification
Pre-glycoprotein polyprotein GP complex
Specific enzymatic cleavages in vivo yield mature proteins. GP-C polyprotein is cleaved in the endoplasmic reticulum by the host protease MBTPS1. Only cleaved glycoprotein is incorporated into virions. The SSP remains stably associated with the GP complex following cleavage by signal peptidase.
Keywords
- PTM
Interaction
Subunit
Glycoprotein G1
Homotrimer; disulfide-linked. In pre-fusion state, G1 homotrimers bind G2 homotrimers via ionic interactions. Part of the GP complex (GP-C) together with glycoprotein G2 and the stable signal peptide. Interacts with the primary host receptor DAG1 on the cell surface; this interaction occurs at pH 8.0 but not at pH 6.0 and below. Upon virus internalization and at endosomal pH, interacts with the host lysosomal protein LAMP1; this interaction mediates G1 dissociation from GP-C and membrane fusion. The GP-complex interacts with protein Z, which interacts with ribonucleocapsid; these interactions may induce virion budding.
Glycoprotein G2
Homotrimer. Interacts with the stable signal peptide. In pre-fusion state, G2 homotrimers bind G1 homotrimers via ionic interactions. Part of the GP complex (GP-C) together with glycoprotein G1 and the stable signal peptide. Acidification in the endosome triggers rearrangements, which ultimately leads to a 6 helix bundle formed by the two heptad repeat domains (HR1 and HR2) in post-fusion state. The GP-complex interacts with protein Z, which interacts with ribonucleocapsid; these interactions may induce virion budding.
Stable signal peptide
Interacts with glycoprotein G2. Part of the GP complex (GP-C) together with glycoprotein G1 and glycoprotein G2. The GP-complex interacts with protein Z, which interacts with ribonucleocapsid; these interactions may induce virion budding.
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 187-215 | Binding to the host receptor LAMP1 | ||||
Sequence: LQTFMRMAWGGSYIALDSGKGSWDCIMTS | ||||||
Region | 257-293 | Fusion | ||||
Sequence: LLGTFTWTLSDSEGNETPGGYCLTRWMLIEAELKCFG | ||||||
Region | 294-362 | HR1 | ||||
Sequence: NTAVAKCNEKHDEEFCDMLRLFDFNKQAIRRLKTEAQMSIQLINKAVNALINDQLIMKNHLRDIMGIPY | ||||||
Region | 367-430 | HR2 | ||||
Sequence: KYWYLNHTVTGKTSLPRCWLVSNGSYLNETHFSDDIEQQADNMITELLQKEYIDRQGKTPLGLV |
Domain
Glycoprotein G1
Upon protonation in a weak acidic environment, the histidine triad involved in host LAMP1 binding inhibits pre-mature triggering of the spike, an inhibition that LAMP1 overrides.
Glycoprotein G2
Contains 1 fusion peptide at the N-terminus, 2 heptad repeats domains HR1 and HR2 and, at the C-terminus, a cytoplasmic domain that plays a role in ER location. Also contains a zinc-binding domain that allows SSP retention in the GPC complex by accepting a cysteine from SSP as the fourth ligand.
Stable signal peptide
The N-terminus is localized at the extracellular side of the GP-C, with a part embedded in the membrane probably.
Sequence similarities
Belongs to the arenaviridae GPC protein family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length490
- Mass (Da)55,712
- Last updated2018-05-23 v1
- ChecksumD6EE98E4F3FF3895