Chinese scientists analyse the structure of NPC1 protein for the first time

Recently, Yan Ning study group at Tsinghua University and academician Gao Fu study group at The Chinese academy of sciences microbial groups worked together to gain a high achievement. They resolved a clear structure of NPC1 protein in the world for the first time and initially revealed its work processes, thus opening a new door for intervening and treating rare genetic disorders such as "Niemann - Pick disease" and Ebola virus.

Professor Yan Ning has been systematically studying Structural biology and biochemistry in the past nine years aiming at regulation pathways of cholesterol metabolism; academician Gao Fu has been engaged in the study of Structural biology of related virus invasion mechanism of major communicable diseases including Ebola. Their collaboratively-completed research paper NPC1 protein-mediated cholesterol transport and Ebola viruses molecular mechanism was published in the journal Cell on May 26. The paper first reported 4.4 Mr Resolution frozen electron microscopic structure of human-derived cholesterol transport protein NPC1 and analyzed to explore the molecular mechanisms NPC1 and collaboration within NPC2 two proteins mediated cholesterol transport. At the same time, it provides a molecular basis for the molecular mechanism of understanding of NPC1 protein mediator Ebola viruses invading.

It is reported that "Niemann - Pick disease" is a class because of rare genetic diseases caused by metabolic aberrations of cholesterol, sphingomyelin and other lipids, and there is no effective treatment for it now. NPC1 exception is the main risk factor of type C "Niemann - Pick disease". Over the past nearly 20 years of genetic and biochemical experiments, researchers found that NPC1 protein is indispensable porter in human cells of cholesterol. If NPC1 mutations happen, it can cause abnormal accumulation of cholesterol in the lysosomes, which may lead to excessive accumulation of lipids of the patients' liver, kidney, spleen and even brain, causing organs lesions and may be fatal. To unlock the mystery of NPC1 mutation causing the unnormal metabolism of cholesterol, to obtain a clear structure NPC1 is a key step. (Want to know other recombinant protein such as Recombinant human Protein and Recombinant Rat Protein?)

According to reports, NPC1 is a membrane protein consists of 1,278 amino acids and contains 13 transmembrane helices. Because of its number of molecule is too small and it is very unstable, making use of electron microscopy to study structural biology is a great challenge. During the process of study, Yan Ning study group developed a new electron microscopy data processing method type of "random phase 3D category", thus analysing this unstable monomer membrane protein structure to 4.4 ? and preliminaryly revealing the melecular mechanism of NPC1 and NPC2 mutual identification and cholesterol transport. In addition, NPC1 is receptor of Ebola virus in human cells, playing an irreplaceable function in the invasion process of Ebola. Yan Ning study group and Gao Fu study group worked together and parsed out frozen electron microscopic structure with a resolution of 6.6 ? of NPC1 and GPcl combination, so as to provide a molecular basis of further studying NPC1 mediated Ebola viruses invading mechanism and how to undermine the recognition interface to conduct intervention.