Abstract
The metastatic invasion of basement membrane by tumor cells involves the binding of tumor cells to laminin. Laminin, a glycoprotein, is a major component of basement membrane. Both tumor and normal cells express a high-affinity receptor for laminin; however, the expression is more pronounced with tumor cells. The pentapeptide, Tyr-Ile-Gly-Ser-Arg, (YIGSR), an amino acid sequence from the B1 chain of laminin, was found to compete with laminin for binding to the laminin receptor. The binding of tumor cells to laminin can be inhibited competitively by YIGSR and, in mice, this has been shown to be translated into a reduction in metastasis. Reports of structural modifications of YIGSR leading to molecules with enhanced activity led us to attempt to learn more about the secondary structure of YIGSR. Through the use of CHARMM, a molecular mechanics program, we were able to discover a conformation of N-acetyl-YIGSR-NHCH3 that is stable over a wide range of dielectric constants. In this conformation the arginine side chain acts to hold Tyr, Ile, and Gly in a partial right-handed alpha helix. We speculate that this partial alpha helical structure is necessary for binding to the lamin receptor and thereby its antimetastatic activity.
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McKelvey, D.R., Brooks, C.L. & Mokotoff, M. A CHARMM analysis of the conformations of the metastasis-inhibiting laminin pentapeptide. J Protein Chem 10, 265–271 (1991). https://doi.org/10.1007/BF01025625
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DOI: https://doi.org/10.1007/BF01025625