Topics

    Integrin-Ligand specificity[Edit]

    Humans have at least 18 α subtypes and 8 β subtypes which together generate 24 known binding pairs for the integrin heterodimer (reviewed in [1, 2]). The α subunit of the integrin heterodimer especially the αI domain determines the ligand specificity for cell-ECM adhesion (reviewed in [3]). The characteristic of integrin subunits is their ability to bind diverse matrix molecules imparted by the heterogeneity of the monomers; this plasticity is instrumental for cell-ECM binding and subsequent mechanotransduction events. 

    The amino acid sequence: arginine-glycine-aspartic acid, or RGD motif, is commonly accepted as a general integrin-binding motif on target ligands, however, individual integrins can also recognize other protein-specific motifs (reviewed in [1, 2, 3]).

    Common ECM components that are bound by integrins (with respective recognition sequence) are

    * Fibronectin (RGD, LDV)
    * Collagen (triple helical GFOGER)
    * Laminin
    * Vitronectin (RGD)
    * Fibrinogen(RGD)
    * Thrombospondin
    * Glycoproteins (e.g. tenascin C, osteopontin, nefronectin)

    Immunologically important integrin ligands are the inter-cellular adhesion molecules (ICAMs), immunoglobulin superfamily members present on inflamed endothelium and antigen-presenting cells.

    Integrins are broadly grouped into four categories based on their ligand-specificity (reviewed in [2]):

    RGD receptors (α5β1, αVβ3, αVβ1,αVβ5, αVβ6, αVβ8, and αIIbβ3)
    Laminin receptors (α1β1, α2β1, α3β1, α6β1, α7β1, and α6β4)
    Leukocyte-specific receptors (αLβ2, αMβ2, αXβ2, and αDβ2)
    Collagen receptors (α1β1, α2β1, α3β1, α10β1, and α11β1)

    References

    1. Barczyk M., Carracedo S., Gullberg D. Integrins. Cell Tissue Res. 2010; 339(1). [PMID: 19693543]
    2. Takada Y., Ye X., Simon S. The integrins. Genome Biol. 2007; 8(5). [PMID: 17543136]
    3. Humphries JD., Byron A., Humphries MJ. Integrin ligands at a glance. J. Cell. Sci. 2006; 119(Pt 19). [PMID: 16988024]
    Updated on: Mon, 20 Oct 2014 09:41:37 GMT