New methods of protein research broaden the molecular basis of diseases

  Understanding protein function at molecular level is the basis of understanding disease The journal Science published the latest research results of the University of Notre Dame research team - how to analyze IDPs   Protein is a three-dimensional structure formed by folding amino acid chain, which is endowed with the shape of interaction with other molecules Most of the proteins are rigid structures, but intrinsic disordered proteins (IDPs) are soft and not folded into regular structures More than 30% of all proteins belong to this kind of disordered protein   The function of IDPs is difficult to understand Their properties like water make it difficult to extract the exact size of proteins and measure the interaction force   "Although the methods of analyzing rigid structural proteins are all excellent, they are not suitable for all protein research What's worse, the two commonly used methods used to study IDPs often produce contradictory results, "said biophysicist Patricia Clark, the author of the article "So, we developed a new analysis program to solve this problem."
In collaboration with Tobin sosnick, a professor in the Department of Biochemistry and molecular biology in Chicago, Clark and others developed a new small angle X-ray scattering (SAXS) analysis method to extract the size of IDPs Protein is placed in the path of X-ray beam The scattering pattern of X-ray includes the size and shape of protein   Compared with the old SAXS method, the new tool has a wider coverage of X-ray scattering mode, which is suitable for computer simulation of IDP structure mode with different levels of confusion   In this paper, the results of IDPs using new SAXS and fluorescence resonance energy transfer (FRET) are discussed   Fret uses fluorescent molecular marker protein to determine the size and shape of IDPs by calculating the distance between fluorescent molecules The researchers found that IDP components interact more strongly with each other than with surrounding molecules, resulting in more collapsed structures   SAXS analysis showed that the soft structure of IDPs was very close to the "real random structure", which could prevent the unnecessary interaction between IDPs and other proteins   Clark said that many diseases, including cancer, are caused by changes in protein properties caused by abnormal mutations, so that proteins cannot interact correctly with themselves or other proteins This study paves the way for the study of folding and misfolding mechanism of IDPs, and creates a new strategy to prevent protein misfolding disease   Although this is a basic work in methodology, its influence level will be very wide.