This entry represents the tail domain of the integrin beta subunit. It forms a four-stranded β-sheet that contains parallel and antiparallel strands and faces an α helix found at the N terminus of this domain [ PUBMED:11546839 ]. Interactions between the α-helix and the β-sheet are mostly hydrophobic and involve a disulphide … expand

This entry represents the tail domain of the integrin beta subunit. It forms a four-stranded β-sheet that contains parallel and antiparallel strands and faces an α helix found at the N terminus of this domain [ PUBMED:11546839 ]. Interactions between the α-helix and the β-sheet are mostly hydrophobic and involve a disulphide bond. The rear of the β sheet is covered with a long A-B loop.

Integrin beta subunits consist of an extracellular domain with a head region, a stalk/leg section, a transmembrane domain, and a cytoplasmic tail. The head region contains a β-I-like domain inserted into a hybrid domain, connected to a plexin-semaphorin-integrin (PSI) [ IPR033760 ]. C-terminal to the PSI domain is an A-domain, which has been predicted to adopt a Rossmann fold similar to that of the alpha subunit, but with additional loops between the second and third β strands. This domain is referred to as VWA [ IPR002369 ]. Many VWA domains bind metal ions via a noncontiguous sequence motif called metal ion-dependent adhesion site (MIDAS) [ PUBMED:9009218 PUBMED:12388743 ]. This is followed by a β-subunit stalk/leg section that contains four cysteine-rich integrin epidermal growth factor-like (I-EGF) modules [ IPR040622 ], [ IPR057073 ], IPR013111 ]. Finally, this is followed by the β-ankle TM domain [ IPR012896 ] and a cytoplasmic tail [ IPR014836 ] [ PUBMED:28510180 ].

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways [ PUBMED:12297042 PUBMED:12361595 ]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal.

Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits [ PUBMED:12234368 ]. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans [ PUBMED:14689578 ]. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule [ PUBMED:2467745 ]. Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.

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