RGD motif

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The tripeptide Arg-Gly-Asp (RGD) consists of Arginine, Glycine, and Aspartate. It was originally identified as the amino acid sequence within the extracellular matrix protein fibronectin that mediates cell attachment. The RGD cell binding sequence has since been identified in other extracellular matrix proteins, including vitronectin and laminin.[1][2] The family of membrane proteins known as integrins act as receptors for these cell adhesion molecules via the RGD motif.[3] A subset of the integrins recognize the RGD motif within their ligands, the binding of which mediates both cell-substratum and cell-cell interactions. These integrins include αvβ3, α5β1 and αIIbβ3.[2]

The RGD domain is both sufficient and indispensable for cell membrane binding.[4] As such, the RGD cell binding motif has supreme relevance in the fields of oncology, tissue engineering and regenerative medicine. Because of their cell-adhesive activity, RGD peptides are frequently incorporated into biomaterials designed to promote wound healing.[5][6] RGD is also an important peptide sequence often used in Targeted therapy. For example, the RGD peptide can be used to target cancer cells on which cell membrane integrins are up-regulated compared to healthy cells.[7]

Though the minimum sequence peptide RGD retains the property of cell adhesion, integrin-RGD bonds are considerably weaker than integrin-fibronectin bonds. The reduced adhesion strength is likely due to both lack of secondary structure and other synergistic domains, namely PHSRN, present in the full-length protein[8]. Furthermore, full length protein domains differentially mediate cell morphology, cell migration and cell proliferation compared to RGD alone.[9]

Other minimum sequence motifs have been identified, including the GFOGER 30 amino acid sequence from collagen 1[10] and the YGISR[11] and A5G81[12] sequences from laminin.

References[edit]

  1. ^ Felding-Habermann B, Cheresh DA (October 1993). "Vitronectin and its receptors". Current Opinion in Cell Biology. 5 (5): 864–8. doi:10.1016/0955-0674(93)90036-p. PMID 7694604. 
  2. ^ a b Ruoslahti E (1988). "Fibronectin and its receptors". Annual Review of Biochemistry. 57: 375–413. doi:10.1146/annurev.bi.57.070188.002111. PMID 2972252. 
  3. ^ Van Agthoven JF, Xiong JP, Alonso JL, Rui X, Adair BD, Goodman SL, Arnaout MA (April 2014). "Structural basis for pure antagonism of integrin αVβ3 by a high-affinity form of fibronectin". Nature Structural & Molecular Biology. 21 (4): 383–8. doi:10.1038/nsmb.2797. PMC 4012256Freely accessible. PMID 24658351. 
  4. ^ Li F, Redick SD, Erickson HP, Moy VT (February 2003). "Force measurements of the alpha5beta1 integrin-fibronectin interaction". Biophysical Journal. 84 (2 Pt 1): 1252–62. doi:10.1016/s0006-3495(03)74940-6. PMC 1302701Freely accessible. PMID 12547805. 
  5. ^ Khan F, Tanaka M, Ahmad SR (2015). "Fabrication of polymeric biomaterials: a strategy for tissue engineering and medical devices". Journal of Materials Chemistry B. 3 (42): 8224–8249. doi:10.1039/c5tb01370d. ISSN 2050-750X. 
  6. ^ Hersel U, Dahmen C, Kessler H (November 2003). "RGD modified polymers: biomaterials for stimulated cell adhesion and beyond". Biomaterials. 24 (24): 4385–415. doi:10.1016/s0142-9612(03)00343-0. PMID 12922151. 
  7. ^ Garanger E, Boturyn D, Dumy P (September 2007). "Tumor targeting with RGD peptide ligands-design of new molecular conjugates for imaging and therapy of cancers". Anti-Cancer Agents in Medicinal Chemistry. 7 (5): 552–8. doi:10.2174/187152007781668706. PMID 17896915. 
  8. ^ Redick SD, Settles DL, Briscoe G, Erickson HP (April 2000). "Defining fibronectin's cell adhesion synergy site by site-directed mutagenesis". The Journal of Cell Biology. 149 (2): 521–7. PMC 2175162Freely accessible. PMID 10769040. 
  9. ^ Fong E, Tirrell DA (December 2010). "Collective cell migration on artificial extracellular matrix proteins containing full-length fibronectin domains". Advanced Materials. 22 (46): 5271–5. doi:10.1002/adma.201002448. PMC 3027490Freely accessible. PMID 20886461. 
  10. ^ Knight CG, Morton LF, Peachey AR, Tuckwell DS, Farndale RW, Barnes MJ (January 2000). "The collagen-binding A-domains of integrins alpha(1)beta(1) and alpha(2)beta(1) recognize the same specific amino acid sequence, GFOGER, in native (triple-helical) collagens". The Journal of Biological Chemistry. 275 (1): 35–40. doi:10.1074/jbc.275.1.35. PMID 10617582. 
  11. ^ Boateng SY, Lateef SS, Mosley W, Hartman TJ, Hanley L, Russell B (January 2005). "RGD and YIGSR synthetic peptides facilitate cellular adhesion identical to that of laminin and fibronectin but alter the physiology of neonatal cardiac myocytes". American Journal of Physiology. Cell Physiology. 288 (1): C30–8. doi:10.1152/ajpcell.00199.2004. PMID 15371257. 
  12. ^ Zhu Y, Cankova Z, Iwanaszko M, Lichtor S, Mrksich M, Ameer GA (June 2018). "Potent laminin-inspired antioxidant regenerative dressing accelerates wound healing in diabetes". Proceedings of the National Academy of Sciences of the United States of America. 115 (26): 6816–6821. doi:10.1073/pnas.1804262115. PMC 6042072Freely accessible. PMID 29891655. 

Further reading[edit]

  • D'Souza SE, Ginsberg MH, Plow EF (July 1991). "Arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif". Trends in Biochemical Sciences. 16 (7): 246–50. PMID 1926332.