Department of Pharmaceutical and Toxicological Chemistry,‘‘Drug Discovery Laboratory’’, University of Naples ‘‘FedericoII’’, Via D. Montesano 49, 80131 Naples, Italy.
Eur Biophys J. 2012 Mar;41(3):353-8. doi: 10.1007/s00249-012-0793-9.
The 37/67-kDa human laminin receptor(LamR) is a cell surface protein that interacts with molecules located in the extra-cellular matrix. In particular, interactions between LamR and laminins play a major role in mediating changes in the cellular environment that affect cell adhesion, neurite outgrowth, tumor growth and metastasis. The exact interaction mode of laminin-1 and LamR is not fully understood. Laminin-1 is thought to bind to LamR through interaction with the so-called peptide G (residues 161–180) and the C-terminal helix (residues 205–229). Here we performed 100-ns atomistic force field based molecular dynamics simulations to explore the structure and dynamics of LamR related to laminin-1 interactions. Our main finding is that loop 188–197 in the C-terminal region is highly flexible. It undergoes a major change resulting in a conformational switch that partially solvent exposes the R180 residue in the final part of the G peptide. So, R180 could contribute to laminin-1 binding. Projection of the simulations along the first two principal components also confirms the importance of this conformational switch in the LamR. This may be a basic prerequisite to clarify the key structural determinants of the interaction of LamR with laminin-1.
37/67kDa 人层粘连蛋白受体（LamR）是一种细胞表面蛋白，与位于细胞外基质中的分子相互作用。特别是，LamR 与层粘连蛋白之间的相互作用在调节影响细胞黏附、轴突生长、肿瘤生长和转移的细胞环境变化方面起着主要作用。层粘连蛋白-1 与 LamR 的确切相互作用模式尚未完全了解。层粘连蛋白-1 被认为通过与所谓的肽 G（残基 161-180）和 C 端螺旋（残基 205-229）的相互作用与 LamR 结合。在这里，我们进行了 100ns 原子力场的分子动力学模拟，以探索与层粘连蛋白-1 相互作用相关的 LamR 的结构和动力学。我们的主要发现是 C 端区域的环 188-197 高度灵活。它发生了重大变化，导致构象转换，使 G 肽的最后部分的 R180 残基部分暴露在溶剂中。因此，R180 可能有助于层粘连蛋白-1 的结合。根据前两个主成分的投影也证实了这种构象转换在 LamR 中的重要性。这可能是阐明 LamR 与层粘连蛋白-1 相互作用的关键结构决定因素的基本前提。
