Proteopedia

5ock

Crystal structure of ACPA E4 in complex with CEP1Crystal structure of ACPA E4 in complex with CEP1

Structural highlights

5ock is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.6Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ENOA_HUMAN Multifunctional enzyme that, as well as its role in glycolysis, plays a part in various processes such as growth control, hypoxia tolerance and allergic responses. May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons. Stimulates immunoglobulin production.[1] [2] [3] [4] [5] MBP1 binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor.[6] [7] [8] [9] [10]

Publication Abstract from PubMed

OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. METHODS: Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. RESULTS: Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. CONCLUSION: These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.

Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies.,Ge C, Xu B, Liang B, Lonnblom E, Lundstrom SL, Zubarev RA, Ayoglu B, Nilsson P, Skogh T, Kastbom A, Malmstrom V, Klareskog L, Toes REM, Rispens T, Dobritzsch D, Holmdahl R Arthritis Rheumatol. 2019 Feb;71(2):210-221. doi: 10.1002/art.40698. Epub 2019, Jan 4. PMID:30152126[11]

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

References

  1. ↑ Ray R, Miller DM. Cloning and characterization of a human c-myc promoter-binding protein. Mol Cell Biol. 1991 Apr;11(4):2154-61. PMID:2005901
  2. ↑ Sugahara T, Nakajima H, Shirahata S, Murakami H. Purification and characterization of immunoglobulin production stimulating factor-II beta derived from Namalwa cells. Cytotechnology. 1992;10(2):137-46. PMID:1369209
  3. ↑ Ghosh AK, Steele R, Ray RB. Functional domains of c-myc promoter binding protein 1 involved in transcriptional repression and cell growth regulation. Mol Cell Biol. 1999 Apr;19(4):2880-6. PMID:10082554
  4. ↑ Feo S, Arcuri D, Piddini E, Passantino R, Giallongo A. ENO1 gene product binds to the c-myc promoter and acts as a transcriptional repressor: relationship with Myc promoter-binding protein 1 (MBP-1). FEBS Lett. 2000 May 4;473(1):47-52. PMID:10802057
  5. ↑ Lopez-Alemany R, Longstaff C, Hawley S, Mirshahi M, Fabregas P, Jardi M, Merton E, Miles LA, Felez J. Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against alpha-Enolase. Am J Hematol. 2003 Apr;72(4):234-42. PMID:12666133 doi:http://dx.doi.org/10.1002/ajh.10299
  6. ↑ Ray R, Miller DM. Cloning and characterization of a human c-myc promoter-binding protein. Mol Cell Biol. 1991 Apr;11(4):2154-61. PMID:2005901
  7. ↑ Sugahara T, Nakajima H, Shirahata S, Murakami H. Purification and characterization of immunoglobulin production stimulating factor-II beta derived from Namalwa cells. Cytotechnology. 1992;10(2):137-46. PMID:1369209
  8. ↑ Ghosh AK, Steele R, Ray RB. Functional domains of c-myc promoter binding protein 1 involved in transcriptional repression and cell growth regulation. Mol Cell Biol. 1999 Apr;19(4):2880-6. PMID:10082554
  9. ↑ Feo S, Arcuri D, Piddini E, Passantino R, Giallongo A. ENO1 gene product binds to the c-myc promoter and acts as a transcriptional repressor: relationship with Myc promoter-binding protein 1 (MBP-1). FEBS Lett. 2000 May 4;473(1):47-52. PMID:10802057
  10. ↑ Lopez-Alemany R, Longstaff C, Hawley S, Mirshahi M, Fabregas P, Jardi M, Merton E, Miles LA, Felez J. Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against alpha-Enolase. Am J Hematol. 2003 Apr;72(4):234-42. PMID:12666133 doi:http://dx.doi.org/10.1002/ajh.10299
  11. ↑ Ge C, Xu B, Liang B, Lonnblom E, Lundstrom SL, Zubarev RA, Ayoglu B, Nilsson P, Skogh T, Kastbom A, Malmstrom V, Klareskog L, Toes REM, Rispens T, Dobritzsch D, Holmdahl R. Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies. Arthritis Rheumatol. 2019 Feb;71(2):210-221. doi: 10.1002/art.40698. Epub 2019, Jan 4. PMID:30152126 doi:http://dx.doi.org/10.1002/art.40698

5ock, resolution 1.60Å

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