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HLA-DM

major histocompatibility complex, class II, DM alpha
2BC4.pdb1.png
Crystallographic structure of human HLA-DM.
Identifiers
Symbol HLA-DMA
Entrez 3108
HUGO 4934
OMIM 142855
RefSeq NM_006120
UniProt P28067
Other data
Locus Chr. 6 p21.3
major histocompatibility complex, class II, DM beta
Identifiers
Symbol HLA-DMB
Entrez 3109
HUGO 4935
OMIM 142856
RefSeq NM_002118
UniProt P28068
Other data
Locus Chr. 6 p21.3

HLA-DM (human leukocyte antigen DM) is an intracellular protein involved in peptide presentation by MHC class II. It is encoded by the genes HLA-DMA and HLA-DMB.

In the endosomes, HLA-DM functions by promoting the dissociation of the CLIP peptide (a place holder peptide) from MHC class II which allows endosomal peptides to bind. Possibly by its preferential binding of the open, peptide-less conformation of MHC class II, HLA-DM then catalyzes peptide exchange, favoring more stable peptide-MHC complexes (which are resistant to DM action). Thus, HLA-DM is thought to play an important role in "editing" the peptide repertoire.

HLA-DM is a protein involved in the immune system. It is a molecular chaperone that works in lysosomes and endosomes. HLA-DM plays a role in the proper loading of peptides and presentation of the peptides in macrophages, dendritic cells, B cells, and other antigen presenting cells. The protein is unable to bind peptides itself, so it interacts with major histocompatibility protein II (MHCII) to speed up the molecule’s binding and releasing of peptides. HLA-DM regulates the peptides that bind to MHCII and present the antigen on antigen presenting cells, therefore controlling which antigen(s) the body mounts an immune response to.

The genes for HLA-DM are located in the MHCII region of the human chromosome 6. The genes code for the alpha and beta chains that makeup the protein. HLA-DM consists of two polymers and three ligands: BETA-D-MANNOSE (BMA), CHLORIDE ION (CL), and 2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE (NDG). The structure of HLA-DM was determined by x-ray diffraction at a resolution of 2.27 Å.

The Ramachandran Plot of HLA-DM can be seen here.

3. Vogt Anne B, Kropshofer Harald (April 1999). "HLA-DM – an endosomal and lysosomal chaperone for the immune system". Trends in Biochemical Sciences. 24 (4): 150-154. doi:10.1016/S0968-0004(99)01364-X



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