Jaseja M, Mergen L, Gillette K, Forbes K, Sehgal I, Copié V
Center for Protease Research, Department of Chemistry and Molecular Biology, North Dakota State University, Fargo, ND 58105, USA.
J Pept Res. 2005 Jul;66(1):9-18. doi: 10.1111/j.1399-3011.2005.00267.x.
Expression of the 37 kDa laminin receptor precursor protein (37LRP) correlates directly with increased invasiveness and the metastatic potential of tumors. The 37LRP matures to a 67 kDa protein which facilitates the binding of cancer cells to basement membranes. The palindrome peptide sequence LMWWML, corresponding to the 173-178-residue stretch of the human 37LRP sequence, has been identified as the laminin-1-binding site. Peptides from 37LRP of species that contain this palindrome-bind laminin-1 with high affinity. Nuclear magnetic resonance (NMR) conformational studies have been undertaken on a synthetic 15-residue peptide (KGAHSVGLMWWMLAR) containing the palindrome to establish the structural basis of this activity. To further correlate the structural data with laminin-1-binding function, analogous structural studies were conducted for a similar peptide (RGKHSIGLIWYLLAR) lacking the palindrome, originating from 37LRP sequence of Saccharomyces cerevisiae and exhibiting low laminin-1-binding affinity. Finally, in vitro cell invasion assays were performed to investigate the possibility that the laminin-1-binding affinity of the peptides influences their inhibitory activity.
37kDa层粘连蛋白受体前体蛋白（37LRP）的表达与肿瘤侵袭性增加及转移潜能直接相关。37LRP成熟为一种67kDa的蛋白，该蛋白有助于癌细胞与基底膜结合。对应于人37LRP序列173 - 178位残基片段的回文肽序列LMWWML已被确定为层粘连蛋白-1结合位点。来自含有此回文序列物种的37LRP的肽与层粘连蛋白-1具有高亲和力结合。已对包含该回文序列的合成15残基肽（KGAHSVGLMWWMLAR）进行了核磁共振（NMR）构象研究，以确定该活性的结构基础。为了进一步将结构数据与层粘连蛋白-1结合功能相关联，对源自酿酒酵母37LRP序列且缺乏回文序列、表现出低层粘连蛋白-1结合亲和力的类似肽（RGKHSIGLIWYLLAR）进行了类似的结构研究。最后，进行了体外细胞侵袭试验，以研究肽的层粘连蛋白-1结合亲和力是否影响其抑制活性。
