Major Histocompatibility complex

What InterPro Tells Us

Below is an example of a human MHC class I protein:

P01892 Human MHC class I antigen A-2 a chain

InterPro Domain Architecture

InterPro Entry	Method Accession	Graphical Match	Method Name
IPR001039	PD000050		MHC_I
IPR001039	PF00129		MHC_I
IPR001039	PR01638		MHCCLASSI
IPR003006	PS00290		IG_MHC
IPR003597	PF07654		C1-set
IPR007110	PS50835		IG_LIKE
IPR010579	PF06623		MHC_I_C
Classification	PDB Chain/Domain ID	PDB Chain/Structural Domains
1oga	1ogaa
3.30.500.10.1	1i4fA1
2.60.40.10.11	1i4fA2
b.1.1.2	d1i4fa1
d.19.1.1	d1i4fa2

From the graphical match above, you can see that the signatures (method accession) are divided into five InterPro entries for human MHC class I A-2 a chain. These entries give information about the domain architecture of the protein, as well as its family relationships.

To explore the family relationships that involve this protein, we need to look at entry IPR003006, which has one signature representing the immunoglobulin/MHC family: PS00290 from the PROSITE database. This signature is based on the C-terminal cysteine involved in an intra-domain disulphide bond that is highly conserved in both immunoglobulin constant chain domains and in an extracellular domain in each type of MHC chain.

The domain architecture of human MHC class I A-2 a chain consists of five domains: three extracellular domains (a-1, a-2 and a-3, where a-1 is at the N-terminus), a transmembrane domain, and a C-terminal tail. IPR001039 represents two extracellular domains, a-1 and a-2, which are located at the N-terminus and which act as the antigen recognition region; this entry is represented by three signatures: PD000050 from the PRODOM database, PF00129 from the PFAM database, and PR01638 from the PRINTS database. IPR003597 represents the third extracellular domain, a-3, and is represented here by one signature, PF07654 from the PFAM database. As the a-3 domain is similar to the immunoglobulin constant chain domain, IPR003597 is found in IPR007110, which represents a broader category for this domain, namely an immunoglobulin-like domain, and which is represented here by one signature, PS50835 from the PROSITE database. The transmembrane domain is not represented in InterPro, because these domains are difficult to produce a signature. Therefore, the area covering the transmembrane domain is seen as a gap in the graphical display between IPR003597 and IPR010579, where IPR010579 represents the C-terminal tail domain that is located intracellularly, and which is represented by one signature, PF06623 from the PFAM database.

The remaining five entries in the table above are from the structural database PDB (green stripe), and from the structural classification databases CATH (pink stripe) and SCOP (black stripe) (the names such as d1i4fa1 are derived from the PDB entry upon which they are based, here PDB entry 1i4f, chain A, region 1). The graphical match for the PDB entry 1ogaa displays the length of the original PDB entry, here covering the entire extracellular region composed of all three domains, a-1, a-2 and a-3. CATH and SCOP both divide the PDB structure into the antigen recognition region composed of domains a-1 and a-2 (1i4fA1 in CATH and d1i4fa2 in SCOP), and the immunoglobulin-like a-3 domain (1i4fA2 in CATH and d1i4fa1 in SCOP). Both CATH and SCOP provide classifications of the PBD structure for these domains.

What the Structure Tells Us

Structures associated with MHC class I A-2 a chain can be viewed using AstexViewer®, which is linked from the Match Table above via the logo on the InterPro page (please note, there is no link directly from this page to the AstexViewer®, therefore you need to go to the link on the InterPro page for P01892). The AstexViewer® displays the PDB structure with the particular CATH or SCOP domain highlighted in yellow.

There are many structures associated with both MHC class I and class II proteins for several different species in the Protein Data Bank (PDB). A detailed description and visualisation of the structural features of MHC class I and II molecules can be found at the PDB ‘Molecule of the Month’. The crystallographic structures of different MHC protein have provided insight into how these molecules can each bind many different antigens, as well as the features that distinguish class I from class II MHC molecules.

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