Comparative Analysis of High-Resolution Structures of Membrane Proteins

This paper presents a statistical analysis and comparison of all existing as of November 20, 2024 membrane protein structures that are represented in the most widely used databases mpstruc, Orientations of Proteins in Membranes (OPM), SCOP and PDBTM, with the total number of structures now reaching 13956. We evaluated the resolution dependencies of structure-derived membrane proteins on their size-related physical characteristics, such as molecular weight, radius and size of the hydrophilic part. Based on the obtained dependencies, we compared the resolving methods of X-ray diffraction and electron microscopy structures, and also compared the methods of protein crystallization in surfo and in meso. The change over time in the number of membrane protein structures obtained by different methods was also examined to analyze trends in structural biology. In 2024, cryo-electron microscopy has emerged as the dominant method, contributing to nearly half of the solved structures, now representing 49.6% of the total. The obtained results demonstrate that the resolution of structures obtained by X-ray diffraction on protein crystals, on average, tends to worsen with increasing protein size, while in electron microscopy, which has recently gained enormous popularity, there is no such trend, but the average resolution is worse. It was also shown that the character of the dependence of resolution on protein size is the same (within error) for the two most common methods of membrane proteins crystallization: in lipid cubic phases (in meso) and in detergent micelles (in surfo). Thus, statistically, neither of these two methods can be considered a priori preferable for achieving better resolution.