ID   CAPSD_FHV               Reviewed;         407 AA.
AC   P12870;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   24-JAN-2024, entry version 120.
DE   RecName: Full=Capsid protein alpha;
DE            EC=3.4.23.44 {ECO:0000269|PubMed:1404613};
DE   Contains:
DE     RecName: Full=Capsid protein beta;
DE     AltName: Full=Coat protein beta;
DE     AltName: Full=Nodavirus endopeptidase;
DE   Contains:
DE     RecName: Full=Membrane-lytic peptide gamma;
DE     AltName: Full=Coat protein gamma;
GN   Name=alpha;
OS   Flock house virus (FHV).
OC   Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Magsaviricetes;
OC   Nodamuvirales; Nodaviridae; Alphanodavirus.
OX   NCBI_TaxID=12287;
OH   NCBI_TaxID=50579; Costelytra zealandica.
OH   NCBI_TaxID=7137; Galleria mellonella (Greater wax moth).
OH   NCBI_TaxID=4513; Hordeum vulgare (Barley).
OH   NCBI_TaxID=4932; Saccharomyces cerevisiae (Baker's yeast).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2798110; DOI=10.1093/nar/17.18.7525;
RA   Dasgupta R., Sgro J.-Y.;
RT   "Nucleotide sequences of three Nodavirus RNA2's: the messengers for their
RT   coat protein precursors.";
RL   Nucleic Acids Res. 17:7525-7526(1989).
RN   [2]
RP   CHARACTERIZATION (CAPSID PROTEIN ALPHA).
RX   PubMed=2116525; DOI=10.1016/0022-2836(90)90191-n;
RA   Kaesberg P., Dasgupta R., Sgro J.-Y., Wery J.-P., Selling B.H., Hosur M.V.,
RA   Johnson J.E.;
RT   "Structural homology among four nodaviruses as deduced by sequencing and X-
RT   ray crystallography.";
RL   J. Mol. Biol. 214:423-435(1990).
RN   [3]
RP   PROTEOLYTIC CLEAVAGE (CAPSID PROTEIN ALPHA), MUTAGENESIS OF ASN-363, AND
RP   CATALYTIC ACTIVITY (CAPSID PROTEIN ALPHA).
RX   PubMed=1404613; DOI=10.1128/jvi.66.11.6728-6734.1992;
RA   Schneemann A., Zhong W., Gallagher T.M., Rueckert R.R.;
RT   "Maturation cleavage required for infectivity of a nodavirus.";
RL   J. Virol. 66:6728-6734(1992).
RN   [4]
RP   FUNCTION (MEMBRANE-LYTIC PEPTIDE GAMMA), AND MUTAGENESIS OF PHE-402;
RP   GLU-403; PHE-405 AND PHE-407.
RX   PubMed=9765417; DOI=10.1128/jvi.72.11.8738-8746.1998;
RA   Schneemann A., Marshall D.;
RT   "Specific encapsidation of nodavirus RNAs is mediated through the C
RT   terminus of capsid precursor protein alpha.";
RL   J. Virol. 72:8738-8746(1998).
RN   [5]
RP   FUNCTION (MEMBRANE-LYTIC PEPTIDE GAMMA), AND PROTEOLYTIC PROCESSING (CAPSID
RP   PROTEIN ALPHA).
RX   PubMed=19553341; DOI=10.1128/jvi.00873-09;
RA   Odegard A.L., Kwan M.H., Walukiewicz H.E., Banerjee M., Schneemann A.,
RA   Johnson J.E.;
RT   "Low endocytic pH and capsid protein autocleavage are critical components
RT   of Flock House virus cell entry.";
RL   J. Virol. 83:8628-8637(2009).
RN   [6]
RP   FUNCTION (MEMBRANE-LYTIC PEPTIDE GAMMA).
RX   PubMed=33853772; DOI=10.1126/sciadv.abe1761;
RA   Jana A.K., May E.R.;
RT   "Atomistic dynamics of a viral infection process: Release of membrane lytic
RT   peptides from a non-enveloped virus.";
RL   Sci. Adv. 7:0-0(2021).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS).
RX   PubMed=8421524; DOI=10.1038/361176a0;
RA   Fisher A.J., Johnson J.E.;
RT   "Ordered duplex RNA controls capsid architecture in an icosahedral animal
RT   virus.";
RL   Nature 361:176-179(1993).
RN   [8] {ECO:0007744|PDB:3LOB}
RP   X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS), AND FUNCTION.
RX   PubMed=20164221; DOI=10.1128/jvi.02670-09;
RA   Banerjee M., Speir J.A., Kwan M.H., Huang R., Aryanpur P.P., Bothner B.,
RA   Johnson J.E.;
RT   "Structure and function of a genetically engineered mimic of a nonenveloped
RT   virus entry intermediate.";
RL   J. Virol. 84:4737-4746(2010).
RN   [9] {ECO:0007744|PDB:4FSJ, ECO:0007744|PDB:4FTB, ECO:0007744|PDB:4FTE, ECO:0007744|PDB:4FTS}
RP   X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1-363 AND 364-407 IN COMPLEX WITH
RP   CA(2+).
RA   Speir J.A., Chen Z., Reddy V.S., Johnson J.E.;
RT   "Structural study of virus assembly intermediates reveals maturation event
RT   sequence and a staging position for externalized lytic peptides.";
RL   Submitted (JUN-2012) to the PDB data bank.
RN   [10] {ECO:0007744|PDB:6ITB, ECO:0007744|PDB:6ITF}
RP   STRUCTURE BY ELECTRON MICROSCOPY (4.70 ANGSTROMS) OF 1-363.
RX   PubMed=31484752; DOI=10.1128/jvi.01115-19;
RA   Azad K., Banerjee M.;
RT   "Structural Dynamics of Nonenveloped Virus Disassembly Intermediates.";
RL   J. Virol. 93:0-0(2019).
CC   -!- FUNCTION: [Capsid protein alpha]: Capsid protein alpha self-assembles
CC       to form an icosahedral procapsid with a T=3 symmetry, about 30 nm in
CC       diameter, and consisting of 60 capsid proteins trimers. In addition,
CC       240 calcium ions are incorporated per capsid during assembly. The
CC       capsid encapsulates the two genomic RNAs. Capsid maturation occurs via
CC       autoproteolytic cleavage of capsid protein alpha generating capsid
CC       protein beta and the membrane-active peptide gamma.
CC       {ECO:0000303|PubMed:31484752}.
CC   -!- FUNCTION: [Membrane-lytic peptide gamma]: Membrane-permeabilizing
CC       peptide produced by virus maturation, thereby creating the infectious
CC       virion (PubMed:33853772). After endocytosis into the host cell, peptide
CC       gamma is probably exposed in endosomes, where it permeabilizes the
CC       endosomal membrane, facilitating translocation of viral capsid or RNA
CC       into the cytoplasm (PubMed:33853772). Involved in specific recognition
CC       and packaging of viral RNA during assembly (PubMed:9765417).
CC       {ECO:0000269|PubMed:33853772, ECO:0000269|PubMed:9765417}.
CC   -!- CATALYTIC ACTIVITY: [Capsid protein beta]:
CC       Reaction=Hydrolysis of an asparaginyl bond involved in the maturation
CC         of the structural protein of the virus, typically -Asn-|-Ala- or
CC         -Asn-|-Phe-.; EC=3.4.23.44; Evidence={ECO:0000269|PubMed:1404613};
CC   -!- SUBCELLULAR LOCATION: [Capsid protein beta]: Virion {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Membrane-lytic peptide gamma]: Virion
CC       {ECO:0000305}. Note=Located inside the capsid and probably externalized
CC       in early endosomes. {ECO:0000305}.
CC   -!- PTM: [Capsid protein alpha]: Capsid protein alpha autocatalytically
CC       maturates into capsid protein beta and peptide gamma.
CC       {ECO:0000269|PubMed:1404613, ECO:0000269|PubMed:19553341}.
CC   -!- SIMILARITY: Belongs to the peptidase A6 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Virus Particle ExploreR db; Note=Icosahedral capsid
CC       structure;
CC       URL="https://viperdb.scripps.edu/Info_Page.php?VDB=fhv";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X15959; CAA34081.1; -; Genomic_RNA.
DR   PIR; B34011; VCBBFH.
DR   RefSeq; NP_689442.1; NC_004144.1.
DR   PDB; 3LOB; X-ray; 3.60 A; A/B/C=1-363, D/E/F=364-407.
DR   PDB; 4FSJ; X-ray; 3.50 A; A/B/C=1-363, D/E/F=364-407.
DR   PDB; 4FTB; X-ray; 2.70 A; A/B/C=1-363, D/E/F=364-407.
DR   PDB; 4FTE; X-ray; 3.50 A; A/B/C=1-407.
DR   PDB; 4FTS; X-ray; 3.20 A; A/B/C=1-407.
DR   PDB; 6ITB; EM; 4.70 A; A/B/C=1-363.
DR   PDB; 6ITF; EM; 4.70 A; A/B/C=1-363.
DR   PDBsum; 3LOB; -.
DR   PDBsum; 4FSJ; -.
DR   PDBsum; 4FTB; -.
DR   PDBsum; 4FTE; -.
DR   PDBsum; 4FTS; -.
DR   PDBsum; 6ITB; -.
DR   PDBsum; 6ITF; -.
DR   EMDB; EMD-9730; -.
DR   SMR; P12870; -.
DR   MEROPS; N01.001; -.
DR   TCDB; 1.A.61.1.2; the insect nodavirus channel-forming chain f (gamma-peptide) family.
DR   GeneID; 962115; -.
DR   KEGG; vg:962115; -.
DR   OrthoDB; 10195at10239; -.
DR   EvolutionaryTrace; P12870; -.
DR   Proteomes; UP000203899; Genome.
DR   GO; GO:0039617; C:T=3 icosahedral viral capsid; IEA:UniProtKB-KW.
DR   GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0039665; P:permeabilization of host organelle membrane involved in viral entry into host cell; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0099008; P:viral entry via permeabilization of inner membrane; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.120.20; -; 1.
DR   InterPro; IPR000696; Peptidase_A6.
DR   InterPro; IPR029053; Viral_coat.
DR   Pfam; PF01829; Peptidase_A6; 1.
DR   PRINTS; PR00863; NODAVIRPTASE.
DR   SUPFAM; SSF88633; Positive stranded ssRNA viruses; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Aspartyl protease; Calcium; Capsid protein; Disulfide bond;
KW   Hydrolase; Metal-binding; Protease; T=3 icosahedral capsid protein;
KW   Viral penetration into host cytoplasm;
KW   Viral penetration via permeabilization of host membrane; Virion;
KW   Virus entry into host cell.
FT   CHAIN           1..407
FT                   /note="Capsid protein alpha"
FT                   /id="PRO_0000402388"
FT   CHAIN           1..363
FT                   /note="Capsid protein beta"
FT                   /id="PRO_0000039194"
FT   CHAIN           364..407
FT                   /note="Membrane-lytic peptide gamma"
FT                   /id="PRO_0000039195"
FT   REGION          1..47
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..29
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        33..47
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        75
FT                   /evidence="ECO:0000305|PubMed:19553341"
FT   BINDING         161
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:4FSJ"
FT   BINDING         161
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0007744|PDB:4FTB, ECO:0007744|PDB:4FTE,
FT                   ECO:0007744|PDB:4FTS"
FT   BINDING         161
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0007744|PDB:4FTS"
FT   BINDING         221
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0007744|PDB:4FTE, ECO:0007744|PDB:4FTS"
FT   BINDING         221
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0007744|PDB:4FTS"
FT   BINDING         221
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0007744|PDB:4FTB"
FT   BINDING         249
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0007744|PDB:4FSJ"
FT   BINDING         251
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0007744|PDB:4FSJ"
FT   BINDING         273
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0007744|PDB:4FTB, ECO:0007744|PDB:4FTE,
FT                   ECO:0007744|PDB:4FTS"
FT   BINDING         273
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0007744|PDB:4FTB"
FT   SITE            363..364
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000269|PubMed:1404613"
FT   SITE            402
FT                   /note="Interaction with viral RNA genome"
FT                   /evidence="ECO:0000269|PubMed:9765417"
FT   SITE            405
FT                   /note="Interaction with viral RNA genome"
FT                   /evidence="ECO:0000269|PubMed:9765417"
FT   SITE            407
FT                   /note="Interaction with viral RNA genome"
FT                   /evidence="ECO:0000269|PubMed:9765417"
FT   DISULFID        69..318
FT   MUTAGEN         363
FT                   /note="N->A,D,T: Prevents maturation cleavage."
FT                   /evidence="ECO:0000269|PubMed:1404613"
FT   MUTAGEN         402
FT                   /note="F->A: Lack in specificity of viral RNA
FT                   encapsidation."
FT                   /evidence="ECO:0000269|PubMed:9765417"
FT   MUTAGEN         403
FT                   /note="E->A: No effect on specificity of viral RNA
FT                   encapsidation."
FT                   /evidence="ECO:0000269|PubMed:9765417"
FT   MUTAGEN         405
FT                   /note="F->A: Lack in specificity of viral RNA
FT                   encapsidation."
FT                   /evidence="ECO:0000269|PubMed:9765417"
FT   MUTAGEN         407
FT                   /note="F->A: Lack in specificity of viral RNA
FT                   encapsidation."
FT                   /evidence="ECO:0000269|PubMed:9765417"
FT   HELIX           61..71
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          76..78
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          90..105
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          109..115
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          121..129
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          139..144
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   HELIX           148..152
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          161..177
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   TURN            181..183
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          187..193
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          196..204
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          210..219
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   HELIX           220..224
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          228..234
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   HELIX           235..237
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          239..242
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          247..249
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          260..263
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   HELIX           269..272
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          275..279
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   TURN            283..285
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          296..302
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          309..323
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   HELIX           329..332
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   HELIX           341..353
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   STRAND          356..358
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   HELIX           360..362
FT                   /evidence="ECO:0007829|PDB:4FTB"
FT   HELIX           367..379
FT                   /evidence="ECO:0007829|PDB:4FTB"
SQ   SEQUENCE   407 AA;  43710 MW;  5A66E01BAD2FEB0B CRC64;
     MVNNNRPRRQ RAQRVVVTTT QTAPVPQQNV PRNGRRRRNR TRRNRRRVRG MNMAALTRLS
     QPGLAFLKCA FAPPDFNTDP GKGIPDRFEG KVVSRKDVLN QSISFTAGQD TFILIAPTPG
     VAYWSASVPA GTFPTSATTF NPVNYPGFTS MFGTTSTSRS DQVSSFRYAS MNVGIYPTSN
     LMQFAGSITV WKCPVKLSTV QFPVATDPAT SSLVHTLVGL DGVLAVGPDN FSESFIKGVF
     SQSACNEPDF EFNDILEGIQ TLPPANVSLG STGQPFTMDS GAEATSGVVG WGNMDTIVIR
     VSAPEGAVNS AILKAWSCIE YRPNPNAMLY QFGHDSPPLD EVALQEYRTV ARSLPVAVIA
     AQNASMWERV KSIIKSSLAA ASNIPGPIGV AASGISGLSA LFEGFGF
//