Integrin beta 7 explained

Integrin beta-7 is an integrin protein that in humans is encoded by the ITGB7 gene.^{[1] [2]} It can pair with ITGA4 (CD49d) to form the heterodimeric integrin receptor αβ, or with ITGAE (CD103) to form αβ.^[3]

Structure

Like all integrin subunits, β is a highly flexible, membrane-bound, extracellular protein that must pair with an α subunit for stability. The molecule's flexibility allows it to dynamically regulate its affinity for ligand through conformational changes.^[4] Beginning with the apical end of the protein, farthest from the cell membrane, the β is composed of a head and upper legs, collectively known as the headpiece, lower legs, a transmembrane domain and a cytoplasmic tail. The top of the head is the I-like domain, sometimes called the βI domain, which, in combination with the α subunit, binds ligand. Just below this is the hybrid domain, a portion of which is N-terminal to the I-like domain. Below the hybrid domain is the PSI domain, which completes the headpiece. The lower legs consist of EGF domains 1-4 and the β tail domain. Finally there is a transmembrane domain, and the C-terminal cytoplasmic tail.^[5]

Interactions

ITGB7 has been shown to interact with EED.^[6]

Further reading

• Rüegg C, Postigo AA, Sikorski EE, Butcher EC, Pytela R, Erle DJ . Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering . The Journal of Cell Biology . 117 . 1 . 179–89 . Apr 1992 . 1372909 . 2289398 . 10.1083/jcb.117.1.179 .
• Chan BM, Elices MJ, Murphy E, Hemler ME . Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of alpha 4 beta 1 (VLA-4) and alpha 4 beta 7 on the human B cell line JY . The Journal of Biological Chemistry . 267 . 12 . 8366–70 . Apr 1992 . 10.1016/S0021-9258(18)42453-2 . 1373725 . free .
• Jiang WM, Jenkins D, Yuan Q, Leung E, Choo KH, Watson JD, Krissansen GW . The gene organization of the human beta 7 subunit, the common beta subunit of the leukocyte integrins HML-1 and LPAM-1 . . 4 . 9 . 1031–40 . Sep 1992 . 1382574 . 10.1093/intimm/4.9.1031 .
• Baker E, Sutherland GR, Jiang WM, Yuan Q, Leung E, Watson JD, Krissansen GW . Grant Robert Sutherland . Mapping of the human integrin beta 7 gene (ITG beta 7) to 12q13.13 by non-isotopic in situ hybridization . Mammalian Genome . 2 . 4 . 272–3 . 1992 . 1543919 . 10.1007/BF00355438 . 30346801 .
• Yuan QA, Jiang WM, Krissansen GW, Watson JD . Cloning and sequence analysis of a novel beta 2-related integrin transcript from T lymphocytes: homology of integrin cysteine-rich repeats to domain III of laminin B chains . International Immunology . 3 . 12 . 1373–4 . Dec 1991 . 1777426 . 10.1093/intimm/3.12.1373 .
• Yuan QA, Jiang WM, Krissansen GW, Watson JD . Cloning and sequence analysis of a novel beta 2-related integrin transcript from T lymphocytes: homology of integrin cysteine-rich repeats to domain III of laminin B chains . International Immunology . 2 . 11 . 1097–108 . 1991 . 2083230 . 10.1093/intimm/2.11.1097 .
• Erle DJ, Brown T, Christian D, Aris R . Lung epithelial lining fluid T cell subsets defined by distinct patterns of beta 7 and beta 1 integrin expression . American Journal of Respiratory Cell and Molecular Biology . 10 . 3 . 237–44 . Mar 1994 . 7509610 . 10.1165/ajrcmb.10.3.7509610 .
• Postigo AA, Sánchez-Mateos P, Lazarovits AI, Sánchez-Madrid F, de Landázuri MO . Alpha 4 beta 7 integrin mediates B cell binding to fibronectin and vascular cell adhesion molecule-1. Expression and function of alpha 4 integrins on human B lymphocytes . Journal of Immunology . 151 . 5 . 2471–83 . Sep 1993 . 10.4049/jimmunol.151.5.2471 . 7689608 . free .
• Shaw SK, Cepek KL, Murphy EA, Russell GJ, Brenner MB, Parker CM . Molecular cloning of the human mucosal lymphocyte integrin alpha E subunit. Unusual structure and restricted RNA distribution . The Journal of Biological Chemistry . 269 . 8 . 6016–25 . Feb 1994 . 10.1016/S0021-9258(17)37563-4 . 8119947 . free .
• Tidswell M, Pachynski R, Wu SW, Qiu SQ, Dunham E, Cochran N, Briskin MJ, Kilshaw PJ, Lazarovits AI, Andrew DP, Butcher EC, Yednock TA, Erle DJ . Structure-function analysis of the integrin beta 7 subunit: identification of domains involved in adhesion to MAdCAM-1 . Journal of Immunology . 159 . 3 . 1497–505 . Aug 1997 . 10.4049/jimmunol.159.3.1497 . 9233649 . free .
• Tan K, Casasnovas JM, Liu JH, Briskin MJ, Springer TA, Wang JH . The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important for integrin recognition . Structure . 6 . 6 . 793–801 . Jun 1998 . 9655832 . 10.1016/S0969-2126(98)00080-X . free .
• Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B . The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins . The Journal of Biological Chemistry . 273 . 42 . 27459–66 . Oct 1998 . 9765275 . 10.1074/jbc.273.42.27459 . free .
• Taraszka KS, Higgins JM, Tan K, Mandelbrot DA, Wang JH, Brenner MB . Molecular basis for leukocyte integrin alpha(E)beta(7) adhesion to epithelial (E)-cadherin . The Journal of Experimental Medicine . 191 . 9 . 1555–67 . May 2000 . 10790430 . 2213439 . 10.1084/jem.191.9.1555 .
• Higgins JM, Cernadas M, Tan K, Irie A, Wang J, Takada Y, Brenner MB . The role of alpha and beta chains in ligand recognition by beta 7 integrins . The Journal of Biological Chemistry . 275 . 33 . 25652–64 . Aug 2000 . 10837471 . 10.1074/jbc.M001228200 . free .
• Puig-Kröger A, Sanz-Rodríguez F, Longo N, Sánchez-Mateos P, Botella L, Teixidó J, Bernabéu C, Corbí AL . Maturation-dependent expression and function of the CD49d integrin on monocyte-derived human dendritic cells . Journal of Immunology . 165 . 8 . 4338–45 . Oct 2000 . 11035069 . 10.4049/jimmunol.165.8.4338 . free .
• Guilliano MJ, Foxx-Orenstein AE, Lebman DA . The microenvironment of human Peyer's patches inhibits the increase in CD38 expression associated with the germinal center reaction . Journal of Immunology . 166 . 4 . 2179–85 . Feb 2001 . 11160270 . 10.4049/jimmunol.166.4.2179 . 36075610 .
• Calderwood DA, Huttenlocher A, Kiosses WB, Rose DM, Woodside DG, Schwartz MA, Ginsberg MH . Increased filamin binding to beta-integrin cytoplasmic domains inhibits cell migration . Nature Cell Biology . 3 . 12 . 1060–8 . Dec 2001 . 11781567 . 10.1038/ncb1201-1060 . 6459957 .
• Calderwood DA, Fujioka Y, de Pereda JM, García-Alvarez B, Nakamoto T, Margolis B, McGlade CJ, Liddington RC, Ginsberg MH . Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling . Proceedings of the National Academy of Sciences of the United States of America . 100 . 5 . 2272–7 . Mar 2003 . 12606711 . 151330 . 10.1073/pnas.262791999 . 2003PNAS..100.2272C . free .

External links

• ITGB7 Info with links in the Cell Migration Gateway

Notes and References

1. Erle DJ, Rüegg C, Sheppard D, Pytela R . Complete amino acid sequence of an integrin beta subunit (beta 7) identified in leukocytes . The Journal of Biological Chemistry . 266 . 17 . 11009–16 . Jun 1991 . 10.1016/S0021-9258(18)99120-9 . 2040616 . free .
2. Web site: Entrez Gene: ITGB7 integrin, beta 7.
3. Byron A, Humphries JD, Askari JA, Craig SE, Mould AP, Humphries MJ . Anti-integrin monoclonal antibodies . Journal of Cell Science . 122 . Pt 22 . 4009–11 . Nov 2009 . 19910492 . 3329622 . 10.1242/jcs.056770 .
4. Carman CV, Springer TA . Integrin avidity regulation: are changes in affinity and conformation underemphasized? . Current Opinion in Cell Biology . 15 . 5 . 547–56 . Oct 2003 . 14519389 . 10.1016/j.ceb.2003.08.003 .
5. Yu Y, Zhu J, Mi LZ, Walz T, Sun H, Chen J, Springer TA . Structural specializations of α(4)β(7), an integrin that mediates rolling adhesion . The Journal of Cell Biology . 196 . 1 . 131–46 . Jan 2012 . 22232704 . 3255974 . 10.1083/jcb.201110023 .
6. Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B . The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins . The Journal of Biological Chemistry . 273 . 42 . 27459–66 . Oct 1998 . 9765275 . 10.1074/jbc.273.42.27459 . free .