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MHC class I peptide loading complex

Definition

Target type: cellularcomponent

A large, multisubunit complex which consists of the MHC class I-beta 2 microglobulin dimer, the transporter associated with antigen presentation (TAP), tapasin (an MHC-encoded membrane protein), the chaperone calreticulin and the thiol oxidoreductase ERp57. Functions in the assembly of peptides with newly synthesized MHC class I molecules. [GOC:jl, PMID:10631934]

The MHC class I peptide loading complex (PLC) is a multi-protein complex that is essential for the generation of MHC class I-restricted peptides, which are displayed on the surface of cells and recognized by cytotoxic T lymphocytes (CTLs). The PLC assembles in the endoplasmic reticulum (ER) and is composed of the following components:

1. **MHC class I heavy chain:** The heavy chain is the main component of the MHC class I molecule, which is a transmembrane protein composed of three alpha domains (α1, α2, and α3) and a transmembrane region. The α1 and α2 domains form the peptide-binding groove that binds to the antigenic peptide. The α3 domain interacts with the β2-microglobulin (β2m) light chain.
2. **β2-microglobulin (β2m):** β2m is a small protein that associates non-covalently with the α3 domain of the MHC class I heavy chain. It is required for proper folding and stability of the MHC class I molecule.
3. **Tapasin:** Tapasin is a chaperone protein that interacts with both the MHC class I heavy chain and the TAP transporter. It assists in the loading of peptides onto the MHC class I molecule by stabilizing the MHC class I-TAP complex and facilitating peptide transfer.
4. **TAP transporter:** The TAP transporter is a heterodimeric transmembrane protein that translocates peptides from the cytosol into the ER lumen. It is composed of two subunits, TAP1 and TAP2, which form a channel through the ER membrane. The TAP transporter preferentially transports peptides of 8-10 amino acids in length, which are typically derived from degraded proteins.
5. **ERp57:** ERp57 is a thiol oxidoreductase that participates in the folding and assembly of MHC class I molecules. It catalyzes disulfide bond formation in the MHC class I heavy chain, which is required for proper folding and stability.

The PLC facilitates peptide loading onto MHC class I molecules in a stepwise manner:

1. **Peptide transport:** Peptides generated in the cytosol are transported into the ER lumen by the TAP transporter.
2. **MHC class I loading:** The TAP transporter delivers peptides to the MHC class I heavy chain, which is associated with β2m and tapasin.
3. **Peptide selection:** Tapasin facilitates the selection of peptides that bind tightly to the MHC class I molecule.
4. **MHC class I assembly:** Once a peptide has bound to the MHC class I molecule, the complex dissociates from tapasin and is transported to the cell surface.

The PLC plays a critical role in the adaptive immune response by ensuring that the MHC class I molecules present a diverse array of peptides to CTLs. This allows CTLs to recognize and eliminate infected or cancerous cells.'
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Proteins (1)

ProteinDefinitionTaxonomy
HLA class I histocompatibility antigen, A alpha chain An MHC class I histocompatibility antigen A alpha chain that is encoded in the genome of human. [PRO:DAN]Homo sapiens (human)

Compounds (8)

CompoundDefinitionClassesRoles
astemizoleastemizole : A piperidine compound having a 2-(4-methoxyphenyl)ethyl group at the 1-position and an N-[(4-fluorobenzyl)benzimidazol-2-yl]amino group at the 4-position.

Astemizole: Antihistamine drug now withdrawn from the market in many countries because of rare but potentially fatal side effects.
benzimidazoles;
piperidines
anti-allergic agent;
anticoronaviral agent;
H1-receptor antagonist
haloperidolhaloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety.

Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)
aromatic ketone;
hydroxypiperidine;
monochlorobenzenes;
organofluorine compound;
tertiary alcohol
antidyskinesia agent;
antiemetic;
dopaminergic antagonist;
first generation antipsychotic;
serotonergic antagonist
spiperonespiperone : An azaspiro compound that is 1,3,8-triazaspiro[4.5]decane which is substituted at positions 1, 4, and 8 by phenyl, oxo, and 4-(p-fluorophenyl)-4-oxobutyl groups, respectively.

Spiperone: A spiro butyrophenone analog similar to HALOPERIDOL and other related compounds. It has been recommended in the treatment of SCHIZOPHRENIA.
aromatic ketone;
azaspiro compound;
organofluorine compound;
piperidines;
tertiary amino compound
alpha-adrenergic antagonist;
antipsychotic agent;
dopaminergic antagonist;
psychotropic drug;
serotonergic antagonist
raloxifene hydrochlorideraloxifene hydrochloride : A hydrochloride salt resulting from the reaction of equimolar amounts of raloxifene and hydrogen chloride.

Raloxifene Hydrochloride: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.
hydrochloridebone density conservation agent;
estrogen antagonist;
estrogen receptor modulator
trazodone hydrochloridetrazodone hydrochloride : A hydrochloride salt prepared from equimolar amounts of trazodone and hydrogen chloride.

Triticum: A plant genus of the family POACEAE that is the source of EDIBLE GRAIN. A hybrid with rye (SECALE CEREALE) is called TRITICALE. The seed is ground into FLOUR and used to make BREAD, and is the source of WHEAT GERM AGGLUTININS.
hydrochlorideadrenergic antagonist;
antidepressant;
H1-receptor antagonist;
sedative;
serotonin uptake inhibitor
doxazosin mesylateCardura: Trade name in United States.methanesulfonate saltgeroprotector
vatalanibmonochlorobenzenes;
phthalazines;
pyridines;
secondary amino compound
angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
vascular endothelial growth factor receptor antagonist
mart-1 antigenMART-1 Antigen: A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.