Protein size and geometry govern mutational robustness
A fundamental question in structural biology centres around understanding protein evolution. Key to this process is mutational robustness, defined as the protein fold's ability to absorb sequence changes without collapsing its structure. Here, we show that robustness is systematically shaped by simple features such as protein size, geometry, and oligomeric state. We used Foldseek-identified…
The fundamental question in structural biology revolves around comprehending protein evolution, with mutational robustness being a crucial aspect. This term refers to a protein's ability to maintain its structure despite sequence alterations. Researchers have now demonstrated that mutational robustness is influenced by fundamental features such as protein size, geometry, and oligomeric state.
By studying Foldseek-identified structural homologs, they quantified family size across monomers and higher-order oligomers. Their findings indicate that proteins within larger families tend to be larger in size, more compact in atomic density, and less soluble. Particularly noteworthy is the observation that homo-oligomers, or proteins composed of multiple subunits, belong to bigger families compared to monomers.
This suggests that the quaternary structure, or the arrangement of subunits, plays a significant role in enhancing mutational tolerance. Furthermore, this robustness signature is linked to an increase in functional complexity, as proteins with adaptive, multifaceted biological roles are more likely to belong to larger structural families than those with specialized functions.
Consequently, this research establishes a structural basis for understanding why certain protein families exhibit extensive diversification while others remain relatively stable over evolutionary time.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
