Plazinski Wojciech, Knys-Dzieciuch Agnieszka
J. Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Krakow, Poland.
Mol Biosyst. 2012 Feb;8(2):543-7. doi: 10.1039/c2mb05399c. Epub 2011 Dec 8.
CD44 is a protein, being a major cell surface receptor for hyaluronan (HA). Molecular modeling investigation was carried out on the murine CD44 in complex with a HA heptasaccharide in order to: (i) elucidate the nature and dynamics of interactions between the HA chain and CD44; (ii) find out if the existence of two conformational forms of CD44 discovered in the XRD (X-Ray Diffraction) study can be responsible for its switching between low and high affinity for HA. The results indicate that the contact of CD44 with HA is dominated by hydrogen bonding with small contribution of hydrophobic interactions and salt bridges. In addition, the two ('A' and 'B') conformational forms of the HA-CD44 complex reported experimentally by Banerji et al. cannot be observed during simulations when considering the distance between HA and the sidechain of the R45 residue. There exists, however, a free energy barrier associated with the change of the φ dihedral angle value at Y46. Additionally, some thermodynamic parameters (e.g. the Gibbs free energy change) accompanying the HA binding by CD44 were estimated.
CD44是一种蛋白质，是透明质酸（HA）的主要细胞表面受体。对与HA七糖复合的小鼠CD44进行了分子建模研究，目的是：（i）阐明HA链与CD44之间相互作用的性质和动力学；（ii）确定在X射线衍射（XRD）研究中发现的CD44的两种构象形式是否可导致其对HA的低亲和力和高亲和力之间的转换。结果表明，CD44与HA的接触主要由氢键主导，疏水相互作用和盐桥的贡献较小。此外，当考虑HA与R45残基侧链之间的距离时，在模拟过程中无法观察到Banerji等人实验报道的HA-CD44复合物的两种（“A”和“B”）构象形式。然而，在Y46处存在与φ二面角值变化相关的自由能垒。此外，还估计了CD44结合HA时伴随的一些热力学参数（例如吉布斯自由能变化）。
