Interaction between Cellobiose Dehydrogenase and Lytic Polysaccharide Monooxygenase

Lytic polysaccharide
monooxygenases (LPMOs) are ubiquitous oxidoreductases,
facilitating the degradation of polymeric carbohydrates in biomass.
Cellobiose dehydrogenase (CDH) is a biologically relevant electron
donor in this process, with the electrons resulting from cellobiose
oxidation being shuttled from the CDH dehydrogenase domain to its
cytochrome domain and then to the LPMO catalytic site. In this work,
we investigate the interaction of four Neurospora crassa LPMOs and five CDH cytochrome domains from different species using
computational methods. We used HADDOCK to perform protein–protein
docking experiments on all 20 combinations and subsequently to select
four complexes for extensive molecular dynamics simulations. The potential
of mean force is computed for a rotation of the cytochrome domain
relative to LPMO. We find that the LPMO loops are largely responsible
for the preferred orientations of the cytochrome domains. This leads
us to postulate a hybrid version of NcLPMO9F, with
exchanged loops and predicted altered cytochrome binding preferences
for this variant. Our work provides insight into the possible mechanisms
of electron transfer between the two protein systems, in agreement
with and complementary to previously published experimental data.

溶菌性多糖单加氧酶（Lytic polysaccharide monooxygenases，LPMOs）是一类广泛分布的氧化还原酶，可介导生物质中聚合糖类的降解。纤维二糖脱氢酶（Cellobiose dehydrogenase，CDH）是该过程中具有生物学相关性的电子供体，纤维二糖氧化产生的电子会从CDH的脱氢酶结构域转移至其细胞色素结构域，随后传递至LPMO的催化位点。本研究采用计算生物学方法，探究了4个粗糙脉孢菌（Neurospora crassa）来源的LPMOs与5个不同物种来源的CDH细胞色素结构域之间的相互作用。本研究使用HADDOCK软件对全部20种组合开展蛋白质-蛋白质对接实验，随后筛选出4个复合物进行系统性分子动力学模拟。研究针对细胞色素结构域相对于LPMO的旋转过程，计算了其平均力势。结果表明，LPMO的环区是决定细胞色素结构域偏好结合取向的核心因素。基于上述发现，本研究推测可构建一种嵌合型NcLPMO9F变体：通过替换其环区，有望改变该变体对细胞色素结构域的结合偏好性。本研究为这两类蛋白质系统间电子转移的潜在机制提供了新的见解，与已发表的实验数据相符且互为补充。