Integrin activation takes shape - PubMed (original) (raw)
Review
Integrin activation takes shape
R C Liddington et al. J Cell Biol. 2002.
Abstract
Integrins are cell surface adhesion receptors that are essential for the development and function of multicellular animals. Here we summarize recent findings on the regulation of integrin affinity for ligand (activation), one mechanism by which cells modulate integrin function. The focus is on the structural basis of integrin activation, the role of the cytoplasmic domain in integrin affinity regulation, and potential mechanisms by which activation signals are propagated from integrin cytoplasmic domains to the extracellular ligand-binding domain.
Figures
Figure 1.
Speculative model of the initial tertiary and quaternary changes during occupancy of activated integrins that lack an α-I domain. Ligand binding to the MIDAS motif of the β-I domain (M) triggers conformational changes in the three MIDAS loops (numbered 1–3) that cause a shift of helix α1 and MIDAS loop 3 toward the βF-α7 loop (black arrows) and a loosening of the contacts between the β-I domain and the propeller. These movements cause steric clashes that are relieved by a rotation of the β-I domain around the indicated pivot point (red circle) at the hybrid–β-I domain boundary, separating the β-I from the propeller. Helix α7 remains in position, thus freeing itself from its contacts with MIDAS loop 3 and helix α1. That is, there is a net shift of helix α7 with respect to the β-I domain as observed in the α-I domain. Since occupancy activates integrins (Du et al., 1993), a reversal of the order of these events could account for integrin activation. In support of this idea, three mutations (B) shown previously to block activation (Baker et al., 1997) define a path between the movement of MIDAS loop 3 and helix α7; an activation epitope maps to the base of α1 (labeled H) at the β-I–hybrid interface. Red highlighted loops on the propeller map the location of chimeras that switch ligand recognition specificities between integrin αv and α5 subunits.
Similar articles
- Integrin activation.
Woodside DG, Liu S, Ginsberg MH. Woodside DG, et al. Thromb Haemost. 2001 Jul;86(1):316-23. Thromb Haemost. 2001. PMID: 11487020 Review. - Talin controls integrin activation.
Calderwood DA. Calderwood DA. Biochem Soc Trans. 2004 Jun;32(Pt3):434-7. doi: 10.1042/BST0320434. Biochem Soc Trans. 2004. PMID: 15157154 Review. - Integrin activation.
Calderwood DA. Calderwood DA. J Cell Sci. 2004 Feb 15;117(Pt 5):657-66. doi: 10.1242/jcs.01014. J Cell Sci. 2004. PMID: 14754902 Review. - The three-dimensional structure of integrins and their ligands, and conformational regulation of cell adhesion.
Springer TA, Wang JH. Springer TA, et al. Adv Protein Chem. 2004;68:29-63. doi: 10.1016/S0065-3233(04)68002-8. Adv Protein Chem. 2004. PMID: 15500858 Review. - Conformational regulation of integrin structure and function.
Shimaoka M, Takagi J, Springer TA. Shimaoka M, et al. Annu Rev Biophys Biomol Struct. 2002;31:485-516. doi: 10.1146/annurev.biophys.31.101101.140922. Epub 2001 Oct 25. Annu Rev Biophys Biomol Struct. 2002. PMID: 11988479 Review.
Cited by
- Integrins and their potential roles in mammalian pregnancy.
Johnson GA, Burghardt RC, Bazer FW, Seo H, Cain JW. Johnson GA, et al. J Anim Sci Biotechnol. 2023 Sep 8;14(1):115. doi: 10.1186/s40104-023-00918-0. J Anim Sci Biotechnol. 2023. PMID: 37679778 Free PMC article. Review. - Integrin Regulators in Neutrophils.
Pulikkot S, Hu L, Chen Y, Sun H, Fan Z. Pulikkot S, et al. Cells. 2022 Jun 25;11(13):2025. doi: 10.3390/cells11132025. Cells. 2022. PMID: 35805108 Free PMC article. Review. - RGD-presenting peptides in amphiphilic and anionic β-sheet hydrogels for improved interactions with cells.
Green H, Ochbaum G, Gitelman-Povimonsky A, Bitton R, Rapaport H. Green H, et al. RSC Adv. 2018 Mar 12;8(18):10072-10080. doi: 10.1039/c7ra12503h. eCollection 2018 Mar 5. RSC Adv. 2018. PMID: 35540811 Free PMC article. - Mechanical regulation of bone remodeling.
Wang L, You X, Zhang L, Zhang C, Zou W. Wang L, et al. Bone Res. 2022 Feb 18;10(1):16. doi: 10.1038/s41413-022-00190-4. Bone Res. 2022. PMID: 35181672 Free PMC article. Review. - Avian Eggshell Membrane as a Novel Biomaterial: A Review.
Shi Y, Zhou K, Li D, Guyonnet V, Hincke MT, Mine Y. Shi Y, et al. Foods. 2021 Sep 14;10(9):2178. doi: 10.3390/foods10092178. Foods. 2021. PMID: 34574286 Free PMC article. Review.
References
- Alonso, J.L., M. Essafi, J.P. Xiong, T. Stehle, and M.A. Arnaout. 2002. Does the integrin alphaa domain act as a ligand for its betaA domain? Curr. Biol. 12:R340–R342. - PubMed
- Armulik, A., I. Nilsson, G. von Heijne, and S. Johansson. 1999. Determination of the border between the transmembrane and cytoplasmic domains of human integrin subunits. J. Biol. Chem. 274:37030–37034. - PubMed
- Bajt, M.L., T. Goodman, and S.L. McGuire. 1995. β2 (CD18) is involved in ligand recognition by I domain integrins, LFA-1 (αLβ2 CD11a/CD18) and MAC-1 (αmβ2 CD11b/CD18). J. Biol. Chem. 270:94–98. - PubMed
- Beer, J.H., K.T. Springer, and B.S. Coller. 1992. Immobilized Arg-Gly-Asp (RGD) peptides of varying lengths as structural probes of the platelet glycoprotein IIb/IIIa receptor. Blood. 79:117–128. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous