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PDBsum entry 1kqr

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Viral protein PDB id
1kqr
Jmol
Contents
Protein chain
160 a.a. *
Ligands
SO4
MNA
GOL
Waters ×190
* Residue conservation analysis
PDB id:
1kqr
Name: Viral protein
Title: Crystal structure of the rhesus rotavirus vp4 sialic acid bi domain in complex with 2-o-methyl-alpha-d-n-acetyl neuramin
Structure: Vp4. Chain: a. Fragment: sialic acid binding domain (residues 62-224). Engineered: yes
Source: Rhesus rotavirus. Organism_taxid: 10969. Gene: segment 4. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
1.40Å     R-factor:   0.169     R-free:   0.181
Authors: P.R.Dormitzer,Z.-Y.J.Sun,G.Wagner,S.C.Harrison
Key ref:
P.R.Dormitzer et al. (2002). The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site. EMBO J, 21, 885-897. PubMed id: 11867517 DOI: 10.1093/emboj/21.5.885
Date:
07-Jan-02     Release date:   27-Mar-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P12473  (VP4_ROTRH) -  Outer capsid protein VP4
Seq:
Struc:
 
Seq:
Struc:
776 a.a.
160 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     viral capsid   1 term 
  Biological process     viral infectious cycle   1 term 

 

 
DOI no: 10.1093/emboj/21.5.885 EMBO J 21:885-897 (2002)
PubMed id: 11867517  
 
 
The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site.
P.R.Dormitzer, Z.Y.Sun, G.Wagner, S.C.Harrison.
 
  ABSTRACT  
 
Cell attachment and membrane penetration are functions of the rotavirus outer capsid spike protein, VP4. An activating tryptic cleavage of VP4 produces the N-terminal fragment, VP8*, which is the viral hemagglutinin and an important target of neutralizing antibodies. We have determined, by X-ray crystallography, the atomic structure of the VP8* core bound to sialic acid and, by NMR spectroscopy, the structure of the unliganded VP8* core. The domain has the beta-sandwich fold of the galectins, a family of sugar binding proteins. The surface corresponding to the galectin carbohydrate binding site is blocked, and rotavirus VP8* instead binds sialic acid in a shallow groove between its two beta-sheets. There appears to be a small induced fit on binding. The residues that contact sialic acid are conserved in sialic acid-dependent rotavirus strains. Neutralization escape mutations are widely distributed over the VP8* surface and cluster in four epitopes. From the fit of the VP8* core into the virion spikes, we propose that VP4 arose from the insertion of a host carbohydrate binding domain into a viral membrane interaction protein.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 The rotavirus triple-layered virion. VP4 and VP7 make up the outer capsid, which constitutes the entry apparatus. The RNA, VP2 and VP6 are the major structural components of the double-layered particle, which is the transcriptionally active core. The line drawing is based on an electron cryomicroscopy-based reconstruction (Yeager et al., 1990).
Figure 6.
Figure 6 Surface representations of the rotavirus VP8^* core, colored according to the variability between the rotavirus strains listed in Table III. Blue represents the most conserved surfaces and red represents the most variable surfaces. Labeled amino acids indicate neutralization escape mutations (Table IV). Labels colored by epitope: 8-1, green; 8-2, blue; 8-3, yellow; 8-4, pink; and not assigned, black. (A) As viewed along arrow 3 of Figure 7. (B) As viewed along arrow 1 and in panel B of Figure 7. (C) As viewed along arrow 2 and in panel C of Figure 7. (A) and (C) are rotated 90° in either direction around the horizontal axis relative to (B), as indicated by arrows on the figure.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2002, 21, 885-897) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22504179 L.Hu, S.E.Crawford, R.Czako, N.W.Cortes-Penfield, D.F.Smith, J.Le Pendu, M.K.Estes, and B.V.Prasad (2012).
Cell attachment protein VP8* of a human rotavirus specifically interacts with A-type histo-blood group antigen.
  Nature, 485, 256-259.
PDB codes: 4drr 4drv 4ds0
22266782 S.D.Trask, S.M.McDonald, and J.T.Patton (2012).
Structural insights into the coupling of virion assembly and rotavirus replication.
  Nat Rev Microbiol, 10, 165-177.  
21157433 E.C.Settembre, J.Z.Chen, P.R.Dormitzer, N.Grigorieff, and S.C.Harrison (2011).
Atomic model of an infectious rotavirus particle.
  EMBO J, 30, 408-416.
PDB codes: 3iyu 3n09
20419315 A.Kuehn, N.Simon, and G.Pradel (2010).
Family members stick together: multi-protein complexes of malaria parasites.
  Med Microbiol Immunol, 199, 209-226.  
20631147 E.Trojnar, P.Otto, B.Roth, J.Reetz, and R.Johne (2010).
The genome segments of a group D rotavirus possess group A-like conserved termini but encode group-specific proteins.
  J Virol, 84, 10254-10265.  
20375171 I.S.Kim, S.D.Trask, M.Babyonyshev, P.R.Dormitzer, and S.C.Harrison (2010).
Effect of mutations in VP5 hydrophobic loops on rotavirus cell entry.
  J Virol, 84, 6200-6207.  
19939934 J.Matthijnssens, Z.F.Taraporewala, H.Yang, S.Rao, L.Yuan, D.Cao, Y.Hoshino, P.P.Mertens, G.R.Carner, M.McNeal, K.Sestak, M.Van Ranst, and J.T.Patton (2010).
Simian rotaviruses possess divergent gene constellations that originated from interspecies transmission and reassortment.
  J Virol, 84, 2013-2026.  
20848863 O.Nakagomi, and T.Nakagomi (2010).
[Toward the elimination of rotavirus gastroenteritis by universal vaccination].
  Uirusu, 60, 33-48.  
20007281 S.D.Trask, I.S.Kim, S.C.Harrison, and P.R.Dormitzer (2010).
A rotavirus spike protein conformational intermediate binds lipid bilayers.
  J Virol, 84, 1764-1770.  
20332209 X.Zhang, M.Boyce, B.Bhattacharya, X.Zhang, S.Schein, P.Roy, and Z.H.Zhou (2010).
Bluetongue virus coat protein VP2 contains sialic acid-binding domains, and VP5 resembles enveloped virus fusion proteins.
  Proc Natl Acad Sci U S A, 107, 6292-6297.
PDB code: 3iyk
19647886 A.Sharma, X.Li, D.S.Bangari, and S.K.Mittal (2009).
Adenovirus receptors and their implications in gene delivery.
  Virus Res, 143, 184-194.  
19692464 J.D.Yoder, S.D.Trask, T.P.Vo, M.Binka, N.Feng, S.C.Harrison, H.B.Greenberg, and P.R.Dormitzer (2009).
VP5* rearranges when rotavirus uncoats.
  J Virol, 83, 11372-11377.  
18974199 M.J.Kraschnefski, A.Bugarcic, F.E.Fleming, X.Yu, M.von Itzstein, B.S.Coulson, and H.Blanchard (2009).
Effects on sialic acid recognition of amino acid mutations in the carbohydrate-binding cleft of the rotavirus spike protein.
  Glycobiology, 19, 194-200.
PDB codes: 2p3i 2p3j 2p3k
19851457 S.M.McDonald, J.Matthijnssens, J.K.McAllen, E.Hine, L.Overton, S.Wang, P.Lemey, M.Zeller, M.Van Ranst, D.J.Spiro, and J.T.Patton (2009).
Evolutionary dynamics of human rotaviruses: balancing reassortment with preferred genome constellations.
  PLoS Pathog, 5, e1000634.  
19342221 T.Stehle, and J.M.Casasnovas (2009).
Specificity switching in virus-receptor complexes.
  Curr Opin Struct Biol, 19, 181-188.  
19157478 U.Neu, T.Stehle, and W.J.Atwood (2009).
The Polyomaviridae: Contributions of virus structure to our understanding of virus receptors and infectious entry.
  Virology, 384, 389-399.  
19036817 Z.Li, M.L.Baker, W.Jiang, M.K.Estes, and B.V.Prasad (2009).
Rotavirus architecture at subnanometer resolution.
  J Virol, 83, 1754-1766.  
18463781 E.E.Espínola, A.Amarilla, J.Arbiza, and G.I.Parra (2008).
Sequence and phylogenetic analysis of the VP4 gene of human rotaviruses isolated in Paraguay.
  Arch Virol, 153, 1067-1073.  
18184711 S.Libersou, X.Siebert, M.Ouldali, L.F.Estrozi, J.Navaza, A.Charpilienne, P.Garnier, D.Poncet, and J.Lepault (2008).
Geometric mismatches within the concentric layers of rotavirus particles: a potential regulatory switch of viral particle transcription activity.
  J Virol, 82, 2844-2852.  
  18540062 X.Yu, A.Guillon, A.J.Szyczew, M.J.Kiefel, B.S.Coulson, M.von Itzstein, and H.Blanchard (2008).
Crystallization and preliminary X-ray diffraction analysis of the carbohydrate-recognizing domain (VP8*) of bovine rotavirus strain NCDV.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 509-511.  
17079279 A.H.Broquet, C.Lenoir, A.Gardet, C.Sapin, S.Chwetzoff, A.M.Jouniaux, S.Lopez, G.Trugnan, M.Bachelet, and G.Thomas (2007).
Hsp70 negatively controls rotavirus protein bioavailability in caco-2 cells infected by the rotavirus RF strain.
  J Virol, 81, 1297-1304.  
17318737 F.E.Fleming, K.L.Graham, K.Taniguchi, Y.Takada, and B.S.Coulson (2007).
Rotavirus-neutralizing antibodies inhibit virus binding to integrins alpha 2 beta 1 and alpha 4 beta 1.
  Arch Virol, 152, 1087-1101.  
17351295 H.M.Bakali, M.D.Herman, K.A.Johnson, A.A.Kelly, A.Wieslander, B.M.Hallberg, and P.Nordlund (2007).
Crystal structure of YegS, a homologue to the mammalian diacylglycerol kinases, reveals a novel regulatory metal binding site.
  J Biol Chem, 282, 19644-19652.
PDB codes: 2bon 2jgr
17135322 O.Delmas, M.Breton, C.Sapin, A.Le Bivic, O.Colard, and G.Trugnan (2007).
Heterogeneity of Raft-type membrane microdomains associated with VP4, the rotavirus spike protein, in Caco-2 and MA 104 cells.
  J Virol, 81, 1610-1618.  
  17277447 Y.D.Zhang, H.Li, H.Liu, and Y.F.Pan (2007).
Expression, purification, crystallization and preliminary X-ray diffraction analysis of the VP8* sialic acid-binding domain of porcine rotavirus strain OSU.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 93-95.  
16415031 A.López-Bueno, M.P.Rubio, N.Bryant, R.McKenna, M.Agbandje-McKenna, and J.M.Almendral (2006).
Host-selected amino acid changes at the sialic acid binding pocket of the parvovirus capsid modulate cell binding affinity and determine virulence.
  J Virol, 80, 1563-1573.  
16511559 J.D.Yoder, and P.R.Dormitzer (2006).
Alternative intermolecular contacts underlie the rotavirus VP5* two- to three-fold rearrangement.
  EMBO J, 25, 1559-1568.
PDB codes: 2b4h 2b4i
16415027 N.Monnier, K.Higo-Moriguchi, Z.Y.Sun, B.V.Prasad, K.Taniguchi, and P.R.Dormitzer (2006).
High-resolution molecular and antigen structure of the VP8* core of a sialic acid-independent human rotavirus strain.
  J Virol, 80, 1513-1523.
PDB code: 2aen
16575520 P.Isa, C.F.Arias, and S.López (2006).
Role of sialic acids in rotavirus infection.
  Glycoconj J, 23, 27-37.  
16971442 S.D.Trask, and P.R.Dormitzer (2006).
Assembly of highly infectious rotavirus particles recoated with recombinant outer capsid proteins.
  J Virol, 80, 11293-11304.  
16327804 S.Spinelli, A.Desmyter, C.T.Verrips, H.J.de Haard, S.Moineau, and C.Cambillau (2006).
Lactococcal bacteriophage p2 receptor-binding protein structure suggests a common ancestor gene with bacterial and mammalian viruses.
  Nat Struct Mol Biol, 13, 85-89.
PDB codes: 2bsd 2bse
15731245 E.E.Rollo, S.J.Hempson, A.Bansal, E.Tsao, I.Habib, S.R.Rittling, D.T.Denhardt, E.R.Mackow, and R.D.Shaw (2005).
The cytokine osteopontin modulates the severity of rotavirus diarrhea.
  J Virol, 79, 3509-3516.  
15642258 F.Mohd Jaafar, H.Attoui, M.W.Bahar, C.Siebold, G.Sutton, P.P.Mertens, P.De Micco, D.I.Stuart, J.M.Grimes, and X.De Lamballerie (2005).
The structure and function of the outer coat protein VP9 of Banna virus.
  Structure, 13, 17-28.
PDB code: 1w9z
16051829 J.A.López, A.J.Maldonado, M.Gerder, J.Abanero, J.Murgich, F.H.Pujol, F.Liprandi, and J.E.Ludert (2005).
Characterization of neuraminidase-resistant mutants derived from rotavirus porcine strain OSU.
  J Virol, 79, 10369-10375.  
15956598 J.B.Pesavento, S.E.Crawford, E.Roberts, M.K.Estes, and B.V.Prasad (2005).
pH-induced conformational change of the rotavirus VP4 spike: implications for cell entry and antibody neutralization.
  J Virol, 79, 8572-8580.  
15890948 M.R.Nokhbeh, S.Hazra, D.A.Alexander, A.Khan, M.McAllister, E.J.Suuronen, M.Griffith, and K.Dimock (2005).
Enterovirus 70 binds to different glycoconjugates containing alpha2,3-linked sialic acid on different cell lines.
  J Virol, 79, 7087-7094.  
  16511112 S.A.Scott, G.Holloway, B.S.Coulson, A.J.Szyczew, M.J.Kiefel, M.von Itzstein, and H.Blanchard (2005).
Crystallization and preliminary X-ray diffraction analysis of the sialic acid-binding domain (VP8*) of porcine rotavirus strain CRW-8.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 617-620.  
14990687 A.Haddad, M.R.Nokhbeh, D.A.Alexander, S.J.Dawe, C.Grisé, N.Gulzar, and K.Dimock (2004).
Binding to decay-accelerating factor is not required for infection of human leukocyte cell lines by enterovirus 70.
  J Virol, 78, 2674-2681.  
15226294 I.Moustafa, H.Connaris, M.Taylor, V.Zaitsev, J.C.Wilson, M.J.Kiefel, M.von Itzstein, and G.Taylor (2004).
Sialic acid recognition by Vibrio cholerae neuraminidase.
  J Biol Chem, 279, 40819-40826.
PDB codes: 1w0o 1w0p
15479820 K.L.Graham, W.Zeng, Y.Takada, D.C.Jackson, and B.S.Coulson (2004).
Effects on rotavirus cell binding and infection of monomeric and polymeric peptides containing alpha2beta1 and alphaxbeta2 integrin ligand sequences.
  J Virol, 78, 11786-11797.  
15329727 P.R.Dormitzer, E.B.Nason, B.V.Prasad, and S.C.Harrison (2004).
Structural rearrangements in the membrane penetration protein of a non-enveloped virus.
  Nature, 430, 1053-1058.
PDB code: 1slq
15452204 S.Zárate, P.Romero, R.Espinosa, C.F.Arias, and S.López (2004).
VP7 mediates the interaction of rotaviruses with integrin alphavbeta3 through a novel integrin-binding site.
  J Virol, 78, 10839-10847.  
15279694 T.Stehle, and T.S.Dermody (2004).
Structural similarities in the cellular receptors used by adenovirus and reovirus.
  Viral Immunol, 17, 129-143.  
15220447 W.P.Burmeister, D.Guilligay, S.Cusack, G.Wadell, and N.Arnberg (2004).
Crystal structure of species D adenovirus fiber knobs and their sialic acid binding sites.
  J Virol, 78, 7727-7736.
PDB codes: 1uxa 1uxb 1uxe
12584352 J.B.Pesavento, A.M.Billingsley, E.J.Roberts, R.F.Ramig, and B.V.Prasad (2003).
Structures of rotavirus reassortants demonstrate correlation of altered conformation of the VP4 spike and expression of unexpected VP4-associated phenotypes.
  J Virol, 77, 3291-3296.  
12915563 S.L.Londrigan, K.L.Graham, Y.Takada, P.Halasz, and B.S.Coulson (2003).
Monkey rotavirus binding to alpha2beta1 integrin requires the alpha2 I domain and is facilitated by the homologous beta1 subunit.
  J Virol, 77, 9486-9501.  
12239329 P.R.Dormitzer, Z.Y.Sun, O.Blixt, J.C.Paulson, G.Wagner, and S.C.Harrison (2002).
Specificity and affinity of sialic acid binding by the rhesus rotavirus VP8* core.
  J Virol, 76, 10512-10517.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.