Modeling and Structure Determination of Homo-Oligomeric Proteins: An Overview of Challenges and Current Approaches

Aljaž Gaber, Miha Pavšič
2021 International Journal of Molecular Sciences  
Protein homo-oligomerization is a very common phenomenon, and approximately half of proteins form homo-oligomeric assemblies composed of identical subunits. The vast majority of such assemblies possess internal symmetry which can be either exploited to help or poses challenges during structure determination. Moreover, aspects of symmetry are critical in the modeling of protein homo-oligomers either by docking or by homology-based approaches. Here, we first provide a brief overview of the nature
more » ... of protein homo-oligomerization. Next, we describe how the symmetry of homo-oligomers is addressed by crystallographic and non-crystallographic symmetry operations, and how biologically relevant intermolecular interactions can be deciphered from the ordered array of molecules within protein crystals. Additionally, we describe the most important aspects of protein homo-oligomerization in structure determination by NMR. Finally, we give an overview of approaches aimed at modeling homo-oligomers using computational methods that specifically address their internal symmetry and allow the incorporation of other experimental data as spatial restraints to achieve higher model reliability.
doi:10.3390/ijms22169081 pmid:34445785 pmcid:PMC8396596 fatcat:yd4qi4zhlbbapfl5v242ml2axy