Page last updated: 2024-10-24

MHC class II protein binding, via antigen binding groove

Definition

Target type: molecularfunction

Binding to the antigen binding groove of major histocompatibility complex class II molecules. [GOC:jl]

MHC class II proteins are crucial for the adaptive immune system's ability to recognize and respond to foreign antigens. They do this by presenting peptide fragments derived from these antigens to T lymphocytes, which are responsible for initiating an immune response. The antigen binding groove, located on the surface of MHC class II molecules, is the key site for this interaction.

The antigen binding groove is a cleft formed by two alpha helices and a beta sheet, situated between the alpha 1 and alpha 2 domains of the MHC class II molecule. It exhibits a remarkable plasticity, allowing it to accommodate peptides of varying lengths and sequences. This flexibility is critical for the MHC class II molecule's ability to bind a wide range of antigens.

The interaction between an antigen peptide and the MHC class II molecule is a complex process driven by multiple factors, including:

* **Non-covalent interactions:** The peptide binds to the MHC class II molecule through a combination of hydrogen bonds, electrostatic interactions, and hydrophobic interactions. These interactions are influenced by the amino acid composition of both the peptide and the MHC class II molecule.
* **Anchor residues:** Specific amino acids within the peptide, known as anchor residues, interact with specific pockets in the antigen binding groove. These interactions are crucial for peptide binding and influence the peptide's affinity for the MHC class II molecule.
* **Conformational changes:** Upon peptide binding, the MHC class II molecule undergoes conformational changes that stabilize the peptide-MHC complex. These changes help to optimize the interaction and enhance the stability of the complex.

The antigen binding groove is thus essential for the MHC class II molecule's ability to present processed peptides to T lymphocytes. This presentation triggers the activation of specific T cells, leading to the development of an immune response against the foreign antigen. This process relies on the groove's flexibility, its ability to engage in diverse interactions, and its conformational adaptability. These features ensure the MHC class II molecule's versatility in presenting a broad range of antigens, crucial for the effective recognition and elimination of pathogens and other foreign entities.'
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Proteins (1)

ProteinDefinitionTaxonomy
HLA class II histocompatibility antigen gamma chainAn MHC class II histocompatibility antigen gamma chain that is encoded in the genome of human. [PRO:WCB, UniProtKB:P04233]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
crizotinibcrizotinib : A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)

Crizotinib: A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER.
3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amineantineoplastic agent;
biomarker;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
pf-06463922lorlatinib : A cyclic ether that is 16,17-dihydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecin-15(10H)-one substituted by methyl groups at positions 2 and 10R, and by cyano, amino and fluoro groups at positions 3, 7 and 12 respectively. It is a small molecule inhibitor of ALK and ROS1 kinase developed by Pfizer for the treatment of ALK-positive non-small cell lung cancer.

lorlatinib: inhibits both anaplastic lymphoma kinase and c-ros oncogene 1 (ROS1) protein
aminopyridine;
aromatic ether;
azamacrocycle;
benzamides;
cyclic ether;
monofluorobenzenes;
nitrile;
organic heterotetracyclic compound;
pyrazoles
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor