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PDBsum entry 2agj
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Immune system PDB id
2agj

 

 

 

 

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Contents
Protein chains
215 a.a. *
226 a.a. *
Ligands
NAG-NAG
Waters ×20
* Residue conservation analysis
PDB id:
2agj
Name: Immune system
Title: Crystal structure of a glycosylated fab from an igm cryoglobulin with properties of a natural proteolytic antibody
Structure: Yvo fab, light chain. Chain: l. Yvo fab, heavy chain. Chain: h
Source: Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
Biol. unit: Dimer (from PQS)
Resolution:
2.60Å     R-factor:   0.219     R-free:   0.279
Authors: P.A.Ramsland,S.S.Terzyan,G.Cloud,C.R.Bourne,W.Farrugia,G.Tribbick, H.M.Geysen,C.R.Moomaw,C.A.Slaughter,A.B.Edmundson
Key ref: P.A.Ramsland et al. (2006). Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody. Biochem J, 395, 473-481. PubMed id: 16422668
Date:
27-Jul-05     Release date:   02-May-06    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q6PJF2  (Q6PJF2_HUMAN) -  IGK@ protein from Homo sapiens
Seq:
Struc: 		235 a.a.
215 a.a.*
Protein chain
Pfam   ArchSchema ?
P01871  (IGHM_HUMAN) -  Immunoglobulin heavy constant mu from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		474 a.a.
226 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 24 residue positions (black crosses)

 

 
Biochem J 395:473-481 (2006)
PubMed id: 16422668  
 
 
Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody.
P.A.Ramsland, S.S.Terzyan, G.Cloud, C.R.Bourne, W.Farrugia, G.Tribbick, H.M.Geysen, C.R.Moomaw, C.A.Slaughter, A.B.Edmundson.
 
  ABSTRACT  
 
The 2.6 A (1 A=0.1 nm) resolution structure has been determined for the glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a subject with Waldenström's macroglobulinaemia. Dynamic light scattering was used to estimate the gel point and monitor the formation of an ordered hydroscopic gel of Yvo IgM upon cooling. If a cryoglobulin forms gels in peripheral tissues and organs, the associated swelling and damage to microvasculature can result in considerable morbidity and mortality. The three-dimensional structure of the branched N-linked oligosaccharide associated with the CH1 domain (first constant domain of heavy chain) is reported. The carbohydrate may act to shield part of the lateral surface of the CH1 domain and crowd the junction between the CH1 and CH2 domains, thereby limiting the segmental flexibility of the Fab arms in intact Yvo IgM, especially at low temperatures. Recently, Yvo IgM was shown to have the properties of a naturally occurring proteolytic antibody [Paul, Karle, Planque, Taguchi, Salas, Nishiyama, Handy, Hunter, Edmundson and Hanson (2004) J. Biol. Chem. 279, 39611-39619; Planque, Bangale, Song, Karle, Taguchi, Poindexter, Bick, Edmundson, Nishiyama and Paul (2004) J. Biol Chem. 279, 14024-14032]. The Yvo protein displayed the ability to cleave, by a nucleophilic mechanism, the amide bonds of a variety of serine protease substrates and the gp120 coat protein of HIV. An atypical serine, arginine and glutamate motif is located in the middle of the Yvo antigen-binding site and displays an overall geometry that mimics the classical serine, histidine and aspartate catalytic triad of serine proteases. Our present findings indicate that pre-existing or natural antibodies can utilize at least one novel strategy for the cleavage of peptide bonds.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21031477 A.S.Kamalanathan, C.Goulvestre, B.Weill, and M.A.Vijayalakshmi (2010).
Proteolysis activity of IgM antibodies from rheumatoid arthritis patients' sera: evidence of atypical catalytic site.
  J Mol Recognit, 23, 577-582.  
20370602 S.Paul, S.Planque, and Y.Nishiyama (2010).
Beneficial catalytic immunity to abeta peptide.
  Rejuvenation Res, 13, 179-187.  
20507874 S.V.Baranova, V.N.Buneva, M.A.Kharitonova, L.P.Sizyakina, C.Calmels, M.L.Andreola, V.Parissi, O.D.Zakharova, and G.A.Nevinsky (2010).
HIV-1 integrase-hydrolyzing IgM antibodies from sera of HIV-infected patients.
  Int Immunol, 22, 671-680.  
19795406 A.Belogurov, A.Kozyr, N.Ponomarenko, and A.Gabibov (2009).
Catalytic antibodies: balancing between Dr. Jekyll and Mr. Hyde.
  Bioessays, 31, 1161-1171.  
19542217 G.Sapparapu, S.A.Planque, Y.Nishiyama, S.K.Foung, and S.Paul (2009).
Antigen-specific proteolysis by hybrid antibodies containing promiscuous proteolytic light chains paired with an antigen-binding heavy chain.
  J Biol Chem, 284, 24622-24633.  
19901987 W.Farrugia, A.M.Scott, and P.A.Ramsland (2009).
A possible role for metallic ions in the carbohydrate cluster recognition displayed by a lewis y specific antibody.
  PLoS One, 4, e7777.
PDB code: 3eyv
18974093 H.Taguchi, S.Planque, G.Sapparapu, S.Boivin, M.Hara, Y.Nishiyama, and S.Paul (2008).
Exceptional Amyloid {beta} Peptide Hydrolyzing Activity of Nonphysiological Immunoglobulin Variable Domain Scaffolds.
  J Biol Chem, 283, 36724-36733.  
18086674 H.Taguchi, S.Planque, Y.Nishiyama, J.Symersky, S.Boivin, P.Szabo, R.P.Friedland, P.A.Ramsland, A.B.Edmundson, M.E.Weksler, and S.Paul (2008).
Autoantibody-catalyzed hydrolysis of amyloid beta peptide.
  J Biol Chem, 283, 4714-4722.  
18486927 H.Taguchi, S.Planque, Y.Nishiyama, P.Szabo, M.E.Weksler, R.P.Friedland, and S.Paul (2008).
Catalytic antibodies to amyloid beta peptide in defense against Alzheimer disease.
  Autoimmun Rev, 7, 391-397.  
18337255 S.Planque, M.A.Escobar, K.C.Smith, H.Taguchi, Y.Nishiyama, E.Donnachie, K.P.Pratt, and S.Paul (2008).
Covalent inactivation of factor VIII antibodies from hemophilia A patients by an electrophilic FVIII Analog.
  J Biol Chem, 283, 11876-11886.  
17617633 K.Trisler, L.L.Looger, V.Sharma, M.Baker, D.E.Benson, S.Trauger, P.G.Schultz, and V.V.Smider (2007).
A metalloantibody that irreversibly binds a protein antigen.
  J Biol Chem, 282, 26344-26353.  
18160012 S.Planque, Y.Mitsuda, H.Taguchi, M.Salas, M.K.Morris, Y.Nishiyama, R.Kyle, P.Okhuysen, M.Escobar, R.Hunter, H.W.Sheppard, C.Hanson, and S.Paul (2007).
Characterization of gp120 hydrolysis by IgA antibodies from humans without HIV infection.
  AIDS Res Hum Retroviruses, 23, 1541-1554.  
17243191 V.Vallas, W.Farrugia, R.L.Raison, A.B.Edmundson, and P.A.Ramsland (2007).
Dissimilar aggregation processes govern precipitation and gelation of human IgM cryoglobulins.
  J Mol Recognit, 20, 90-96.  
17914190 Y.Mitsuda, S.Planque, M.Hara, R.Kyle, H.Taguchi, Y.Nishiyama, and S.Paul (2007).
Naturally occurring catalytic antibodies: evidence for preferred development of the catalytic function in IgA class antibodies.
  Mol Biotechnol, 36, 113-122.  
17728243 Y.Nishiyama, Y.Mitsuda, H.Taguchi, S.Planque, M.Salas, C.V.Hanson, and S.Paul (2007).
Towards covalent vaccination: improved polyclonal HIV neutralizing antibody response induced by an electrophilic gp120 V3 peptide analog.
  J Biol Chem, 282, 31250-31256.  
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 code is shown on the right.

 

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