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PDBsum entry 2wbw

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protein ligands metals Protein-protein interface(s) links
Structural protein PDB id
2wbw

 

 

 

 

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Contents
Protein chains
182 a.a. *
120 a.a. *
Ligands
SIA
Metals
_CA
Waters ×400
* Residue conservation analysis
PDB id:
2wbw
Name: Structural protein
Title: Ad37 fibre head in complex with car d1 and sialic acid
Structure: Fiber protein. Chain: a. Fragment: fibre head, residues 22-210. Synonym: human adenovirus type 37 fibre head. Engineered: yes. Coxsackievirus and adenovirus receptor. Chain: b. Fragment: d1, residues 15-140. Synonym: coxsackievirus b-adenovirus receptor, hcvadr, cvb3-binding
Source: Human adenovirus 37. Organism_taxid: 52275. Expressed in: escherichia coli. Expression_system_taxid: 511693. Homo sapiens. Human. Organism_taxid: 9606.
Resolution:
1.55Å     R-factor:   0.171     R-free:   0.176
Authors: E.Seiradake,D.Henaff,H.Wodrich,O.Billet,M.Perreau,C.Hippert, F.Mennechet,G.Schoehn,H.Lortat-Jacob,H.Dreja,S.Ibanes,V.Kalatzis, J.P.Wang,R.W.Finberg,S.Cusack,E.J.Kremer
Key ref: E.Seiradake et al. (2009). The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution. Plos Pathog, 5, e1000277. PubMed id: 19119424
Date:
05-Mar-09     Release date:   17-Mar-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q64823  (Q64823_9ADEN) -  Fiber from Human adenovirus D37
Seq:
Struc:
365 a.a.
182 a.a.
Protein chain
Pfam   ArchSchema ?
P78310  (CXAR_HUMAN) -  Coxsackievirus and adenovirus receptor from Homo sapiens
Seq:
Struc:
365 a.a.
120 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
Plos Pathog 5:e1000277 (2009)
PubMed id: 19119424  
 
 
The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution.
E.Seiradake, D.Henaff, H.Wodrich, O.Billet, M.Perreau, C.Hippert, F.Mennechet, G.Schoehn, H.Lortat-Jacob, H.Dreja, S.Ibanes, V.Kalatzis, J.P.Wang, R.W.Finberg, S.Cusack, E.J.Kremer.
 
  ABSTRACT  
 
Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad-erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a mechanism that may explain the biodistribution and pathogenic inconsistencies found between human and animal models.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21198670 B.S.Graham (2011).
Biological challenges and technological opportunities for respiratory syncytial virus vaccine development.
  Immunol Rev, 239, 149-166.  
21366418 D.Henaff, S.Salinas, and E.J.Kremer (2011).
An adenovirus traffic update: from receptor engagement to the nuclear pore.
  Future Microbiol, 6, 179-192.  
  20615244 C.Lyle, and F.McCormick (2010).
Integrin alphavbeta5 is a primary receptor for adenovirus in CAR-negative cells.
  Virol J, 7, 148.  
20118368 I.von Ossowski, J.Reunanen, R.Satokari, S.Vesterlund, M.Kankainen, H.Huhtinen, S.Tynkkynen, S.Salminen, W.M.de Vos, and A.Palva (2010).
Mucosal adhesion properties of the probiotic Lactobacillus rhamnosus GG SpaCBA and SpaFED pilin subunits.
  Appl Environ Microbiol, 76, 2049-2057.  
19788385 J.S.Senac, K.Doronin, S.J.Russell, D.F.Jelinek, P.R.Greipp, and M.A.Barry (2010).
Infection and killing of multiple myeloma by adenoviruses.
  Hum Gene Ther, 21, 179-190.  
19947826 J.de Vrij, R.A.Willemsen, L.Lindholm, R.C.Hoeben, C.H.Bangma, C.Barber, J.P.Behr, S.Briggs, R.Carlisle, W.S.Cheng, I.J.Dautzenberg, C.de Ridder, H.Dzojic, P.Erbacher, M.Essand, K.Fisher, A.Frazier, L.J.Georgopoulos, I.Jennings, S.Kochanek, D.Koppers-Lalic, R.Kraaij, F.Kreppel, M.Magnusson, N.Maitland, P.Neuberg, R.Nugent, M.Ogris, J.S.Remy, M.Scaife, E.Schenk-Braat, E.Schooten, L.Seymour, M.Slade, P.Szyjanowicz, T.Totterman, T.G.Uil, K.Ulbrich, L.van der Weel, W.van Weerden, E.Wagner, and G.Zuber (2010).
Adenovirus-derived vectors for prostate cancer gene therapy.
  Hum Gene Ther, 21, 795-805.  
20610817 R.Alba, A.C.Bradshaw, L.Coughlan, L.Denby, R.A.McDonald, S.N.Waddington, S.M.Buckley, J.A.Greig, A.L.Parker, A.M.Miller, H.Wang, A.Lieber, N.van Rooijen, J.H.McVey, S.A.Nicklin, and A.H.Baker (2010).
Biodistribution and retargeting of FX-binding ablated adenovirus serotype 5 vectors.
  Blood, 116, 2656-2664.  
19711370 A.K.Zaiss, H.B.Machado, and H.R.Herschman (2009).
The influence of innate and pre-existing immunity on adenovirus therapy.
  J Cell Biochem, 108, 778-790.  
19485756 E.E.Thacker, L.Timares, and Q.L.Matthews (2009).
Strategies to overcome host immunity to adenovirus vectors in vaccine development.
  Expert Rev Vaccines, 8, 761-777.  
19643990 E.J.Kremer (2009).
Mutagenesis of hexon "FX" hepatic tropism.
  Blood, 114, 929-930.  
19655763 L.M.Kasman, S.Barua, P.Lu, K.Rege, and C.Voelkel-Johnson (2009).
Polymer-enhanced adenoviral transduction of CAR-negative bladder cancer cells.
  Mol Pharm, 6, 1612-1619.  
19348049 L.W.Seymour, and K.D.Fisher (2009).
Preclinical screening of gene therapy in human tissues.
  Hum Gene Ther, 20, 291-292.  
19506548 M.S.Veena, M.Qin, A.Andersson, S.Sharma, and R.K.Batra (2009).
CAR mediates efficient tumor engraftment of mesenchymal type lung cancer cells.
  Lab Invest, 89, 875-886.  
  19222836 N.Shimony, G.Elkin, D.Kolodkin-Gal, L.Krasny, S.Urieli-Shoval, and Y.S.Haviv (2009).
Analysis of adenoviral attachment to human platelets.
  Virol J, 6, 25.  
19429866 R.Alba, A.C.Bradshaw, A.L.Parker, D.Bhella, S.N.Waddington, S.A.Nicklin, N.van Rooijen, J.Custers, J.Goudsmit, D.H.Barouch, J.H.McVey, and A.H.Baker (2009).
Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: effect of mutagenesis on FX interactions and gene transfer.
  Blood, 114, 965-971.  
19461877 S.Salinas, L.G.Bilsland, D.Henaff, A.E.Weston, A.Keriel, G.Schiavo, and E.J.Kremer (2009).
CAR-associated vesicular transport of an adenovirus in motor neuron axons.
  PLoS Pathog, 5, e1000442.  
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.

 

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