5ni9

Structural highlights

Function

[DRA_HUMAN] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading. [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]} [2B14_HUMAN] Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.

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. ↑ Pieper J, Dubnovitsky A, Gerstner C, James EA, Rieck M, Kozhukh G, Tandre K, Pellegrino S, Gebe JA, Ronnblom L, Sandalova T, Kwok WW, Klareskog L, Buckner JH, Achour A, Malmstrom V. Memory T cells specific to citrullinated alpha-enolase are enriched in the rheumatic joint. J Autoimmun. 2018 May 28. pii: S0896-8411(18)30128-8. doi:, 10.1016/j.jaut.2018.04.004. PMID:29853344 doi:http://dx.doi.org/10.1016/j.jaut.2018.04.004