Study On The Three-dimensional Structure Of Adenovirus By Cryo-EM Local Reconstruction

The structure of matter determines the function of matter.The same is true of biological macromolecules.As a special biological macromolecule,viruses are widely distributed in nature.They must be stored in living cells,although viruses will bring some useful benefits to humans.Place,but more often it brings extremely dangerous diseases.Structural analysis is the basis for studying virus-related functions.Therefore,studying the structure of viruses is of great significance.The main research methods of structural biology include nuclear magnetic resonance spectroscopy(NMR),X-ray crystallography,and cryo-electron microscopy(Cryo-EM).Among them,cryo-electron microscopy has unique advantages in analyzing the structure of biological macromolecules.The sample does not need to be crystallized during sample preparation,which can make the sample closer to its active state,and is suitable for larger molecular weight biological macromolecules.After years of development,cryo-electron microscopy technology has become increasingly mature and achieved breakthrough progress.Cryo-electron microscopy has developed into the most powerful tool for analyzing the structure of biological macromolecules in structural biology.The large molecular weight of virus particles makes the process of virus crystallization very difficult.Cryoelectron microscopy has become the most powerful tool for analyzing virus structure because it does not need to crystallize the sample.Viral particles generally have a high degree of symmetry(such as icosahedron symmetry).This characteristicis used in the reconstruction process to suppress image noise and improve the resolution of the final reconstruction.Cryo-electron microscopy single particle technology is becoming more and more mature,which can resolve the high-resolution three-dimensional structure of the virus.However,there are still many problems.The resolution of various regions on the viral capsid cannot be consistent,and the resolution of some flexible proteins often does not reach the resolution of the capsid.In order to solve this series of problems,this paper proposes a new local reconstruction method based on cryo-electron icosahedron three-dimensional reconstruction.The flexible protein region is locally refined and reconstructed to obtain a high-resolution flexible protein structure.The main work of this paper is as follows: 1)A high-resolution structure of human adenovirus capsid 3.4? was obtained by using icosahedron three-dimensional reconstruction technology,and an atomic model was constructed;2)methods and local refinement Principle introduction.3)Analysis of the flexible protein structure on the human adenovirus capsid,the high-resolution structure of the flexible protein was obtained,and the atomic model was modified.