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{{STRUCTURE_3dpr| PDB=3dpr | SCENE=  }}
==Human rhinovirus 2 bound to a concatamer of the VLDL receptor module V3==
===Human rhinovirus 2 bound to a concatamer of the VLDL receptor module V3===
<StructureSection load='3dpr' size='340' side='right' caption='[[3dpr]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
{{ABSTRACT_PUBMED_19073182}}
== Structural highlights ==
<table><tr><td colspan='2'>[[3dpr]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_rhinovirus_a2 Human rhinovirus a2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DPR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3DPR FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3dpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dpr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3dpr RCSB], [http://www.ebi.ac.uk/pdbsum/3dpr PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/VLDLR_HUMAN VLDLR_HUMAN]] Defects in VLDLR are the cause of cerebellar ataxia mental retardation and dysequilibrium syndrome type 1 (CMARQ1) [MIM:[http://omim.org/entry/224050 224050]]; also known as dysequilibrium syndrome (DES) or non-progressive cerebellar disorder with mental retardation. CMARQ1 is a congenital, non-progressive cerebellar ataxia associated with disturbed equilibrium, delayed ambulation, mental retardation and cerebellar hypoplasia. Additional features include short stature, strabismus, pes planus and, rarely, seizures.<ref>PMID:16080122</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/POLG_HRV2 POLG_HRV2]] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with human VLDLR to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm.<ref>PMID:11034318</ref> <ref>PMID:12191477</ref>  VP0 precursor is a component of immature procapsids (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref>  Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription.<ref>PMID:11034318</ref> <ref>PMID:12191477</ref>  Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref>  Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref>  Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref>  Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref>  RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).<ref>PMID:11034318</ref> <ref>PMID:12191477</ref>  [[http://www.uniprot.org/uniprot/VLDLR_HUMAN VLDLR_HUMAN]] Binds VLDL and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Binding to Reelin induces tyrosine phosphorylation of Dab1 and modulation of Tau phosphorylation (By similarity).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dp/3dpr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
X-ray structures of human rhinovirus 2 (HRV2) in complex with soluble very-low-density lipoprotein receptors encompassing modules 1, 2, and 3 (V123) and five V3 modules arranged in tandem (V33333) demonstrates multi-modular binding around the virion's five-fold axes. Occupancy was 60% for V123 and 100% for V33333 explaining the high-avidity of the interaction. Surface potentials of 3D-models of all minor group HRVs and K-type major group HRVs were compared; hydrophobic interactions between a conserved lysine in the viruses and a tryptophan in the receptor modules together with coulombic attraction via diffuse opposite surface potentials determine minor group HRV receptor specificity.


==Disease==
Minor group human rhinovirus-receptor interactions: geometry of multimodular attachment and basis of recognition.,Querol-Audi J, Konecsni T, Pous J, Carugo O, Fita I, Verdaguer N, Blaas D FEBS Lett. 2009 Jan 5;583(1):235-40. Epub 2008 Dec 13. PMID:19073182<ref>PMID:19073182</ref>
[[http://www.uniprot.org/uniprot/VLDLR_HUMAN VLDLR_HUMAN]] Defects in VLDLR are the cause of cerebellar ataxia mental retardation and dysequilibrium syndrome type 1 (CMARQ1) [MIM:[http://omim.org/entry/224050 224050]]; also known as dysequilibrium syndrome (DES) or non-progressive cerebellar disorder with mental retardation. CMARQ1 is a congenital, non-progressive cerebellar ataxia associated with disturbed equilibrium, delayed ambulation, mental retardation and cerebellar hypoplasia. Additional features include short stature, strabismus, pes planus and, rarely, seizures.<ref>PMID:16080122</ref>  


==Function==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[http://www.uniprot.org/uniprot/POLG_HRV2 POLG_HRV2]] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with human VLDLR to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm.<ref>PMID:11034318</ref><ref>PMID:12191477</ref>  VP0 precursor is a component of immature procapsids (By similarity).<ref>PMID:11034318</ref><ref>PMID:12191477</ref>  Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription.<ref>PMID:11034318</ref><ref>PMID:12191477</ref>  Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).<ref>PMID:11034318</ref><ref>PMID:12191477</ref>  Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).<ref>PMID:11034318</ref><ref>PMID:12191477</ref>  Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).<ref>PMID:11034318</ref><ref>PMID:12191477</ref>  Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).<ref>PMID:11034318</ref><ref>PMID:12191477</ref>  RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).<ref>PMID:11034318</ref><ref>PMID:12191477</ref> [[http://www.uniprot.org/uniprot/VLDLR_HUMAN VLDLR_HUMAN]] Binds VLDL and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Binding to Reelin induces tyrosine phosphorylation of Dab1 and modulation of Tau phosphorylation (By similarity).
</div>


==About this Structure==
==See Also==
[[3dpr]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Human_rhinovirus_a2 Human rhinovirus a2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DPR OCA].
*[[Human rhinovirus|Human rhinovirus]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:019073182</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Human rhinovirus a2]]
[[Category: Human rhinovirus a2]]
[[Category: Fita, I.]]
[[Category: Fita, I]]
[[Category: Pous, J.]]
[[Category: Pous, J]]
[[Category: Querol-Audi, J.]]
[[Category: Querol-Audi, J]]
[[Category: Verdaguer, N.]]
[[Category: Verdaguer, N]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]
[[Category: Capsid protein]]
[[Category: Capsid protein]]

Revision as of 02:20, 4 January 2015

Human rhinovirus 2 bound to a concatamer of the VLDL receptor module V3Human rhinovirus 2 bound to a concatamer of the VLDL receptor module V3

Structural highlights

3dpr is a 5 chain structure with sequence from Homo sapiens and Human rhinovirus a2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Resources:FirstGlance, OCA, RCSB, PDBsum

Disease

[VLDLR_HUMAN] Defects in VLDLR are the cause of cerebellar ataxia mental retardation and dysequilibrium syndrome type 1 (CMARQ1) [MIM:224050]; also known as dysequilibrium syndrome (DES) or non-progressive cerebellar disorder with mental retardation. CMARQ1 is a congenital, non-progressive cerebellar ataxia associated with disturbed equilibrium, delayed ambulation, mental retardation and cerebellar hypoplasia. Additional features include short stature, strabismus, pes planus and, rarely, seizures.[1]

Function

[POLG_HRV2] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with human VLDLR to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm.[2] [3] VP0 precursor is a component of immature procapsids (By similarity).[4] [5] Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription.[6] [7] Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).[8] [9] Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).[10] [11] Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity).[12] [13] Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).[14] [15] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).[16] [17] [VLDLR_HUMAN] Binds VLDL and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Binding to Reelin induces tyrosine phosphorylation of Dab1 and modulation of Tau phosphorylation (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

X-ray structures of human rhinovirus 2 (HRV2) in complex with soluble very-low-density lipoprotein receptors encompassing modules 1, 2, and 3 (V123) and five V3 modules arranged in tandem (V33333) demonstrates multi-modular binding around the virion's five-fold axes. Occupancy was 60% for V123 and 100% for V33333 explaining the high-avidity of the interaction. Surface potentials of 3D-models of all minor group HRVs and K-type major group HRVs were compared; hydrophobic interactions between a conserved lysine in the viruses and a tryptophan in the receptor modules together with coulombic attraction via diffuse opposite surface potentials determine minor group HRV receptor specificity.

Minor group human rhinovirus-receptor interactions: geometry of multimodular attachment and basis of recognition.,Querol-Audi J, Konecsni T, Pous J, Carugo O, Fita I, Verdaguer N, Blaas D FEBS Lett. 2009 Jan 5;583(1):235-40. Epub 2008 Dec 13. PMID:19073182[18]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Boycott KM, Flavelle S, Bureau A, Glass HC, Fujiwara TM, Wirrell E, Davey K, Chudley AE, Scott JN, McLeod DR, Parboosingh JS. Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification. Am J Hum Genet. 2005 Sep;77(3):477-83. Epub 2005 Jul 22. PMID:16080122 doi:S0002-9297(07)63027-4
  2. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
  3. ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
  4. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
  5. ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
  6. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
  7. ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
  8. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
  9. ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
  10. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
  11. ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
  12. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
  13. ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
  14. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
  15. ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
  16. ↑ Glaser W, Skern T. Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro. FEBS Lett. 2000 Sep 1;480(2-3):151-5. PMID:11034318
  17. ↑ Hewat EA, Neumann E, Blaas D. The concerted conformational changes during human rhinovirus 2 uncoating. Mol Cell. 2002 Aug;10(2):317-26. PMID:12191477
  18. ↑ Querol-Audi J, Konecsni T, Pous J, Carugo O, Fita I, Verdaguer N, Blaas D. Minor group human rhinovirus-receptor interactions: geometry of multimodular attachment and basis of recognition. FEBS Lett. 2009 Jan 5;583(1):235-40. Epub 2008 Dec 13. PMID:19073182 doi:10.1016/j.febslet.2008.12.014

3dpr, resolution 3.50Å

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