6LLQ

Solution NMR structure of de novo Rossmann2x2 fold with most of the core mutated to valine, R2x2_VAL88

Summary for 6LLQ

• Entry DOI: 10.2210/pdb6llq/pdb
• Descriptor: VAL88 (1 entity in total)
• Functional Keywords: de novo design, de novo protein
• Biological source: unidentified
• Total number of polymer chains: 1
• Total formula weight: 11105.69

Authors

Kobayashi, N.,Sugiki, T.,Fujiwara, T.,Koga, R.,Yamamoto, M.,Kosugi, T.,Koga, N. (deposition date: 2019-12-23, release date: 2020-12-02, Last modification date: 2024-05-15)

Primary citation

Koga, R.,Yamamoto, M.,Kosugi, T.,Kobayashi, N.,Sugiki, T.,Fujiwara, T.,Koga, N.
Robust folding of a de novo designed ideal protein even with most of the core mutated to valine.
Proc.Natl.Acad.Sci.USA, 117:31149-31156, 2020

PubMed Abstract: Protein design provides a stringent test for our understanding of protein folding. We previously described principles for designing ideal protein structures stabilized by consistent local and nonlocal interactions, based on a set of rules relating local backbone structures to tertiary packing motifs. The principles have made possible the design of protein structures having various topologies with high thermal stability. Whereas nonlocal interactions such as tight hydrophobic core packing have traditionally been considered to be crucial for protein folding and stability, the rules proposed by our previous studies suggest the importance of local backbone structures to protein folding. In this study, we investigated the robustness of folding of de novo designed proteins to the reduction of the hydrophobic core, by extensive mutation of large hydrophobic residues (Leu, Ile) to smaller ones (Val) for one of the designs. Surprisingly, even after 10 Leu and Ile residues were mutated to Val, this mutant with the core mostly filled with Val was found to not be in a molten globule state and fold into the same backbone structure as the original design, with high stability. These results indicate the importance of local backbone structures to the folding ability and high thermal stability of designed proteins and suggest a method for engineering thermally stabilized natural proteins.

PubMed: 33229587
DOI: 10.1073/pnas.2002120117

Experimental method

SOLUTION NMR