Folding Mechanisms of Small Proteins GB1 and LB1

Abstract

The B1 domains of protein G (GB1) and protein L (LB1) are two small proteins that binds to antibody immunoglobulin G (IgG). GB1 and LB1 are similar in size (about 60 residues), and also have an overall similar structure (β-hairpin--α-helix--β-hairpin). However their sequences are very different, possessing only 15% identity in a structure-based alignment. Therefore, there are interesting similarity and differences in their folding mechanisms. Experimental evidence indicated that LB1 folds in a two-state manner; while GB1 folds in a more complex way -- an early stage intermediate may exist in the folding path. Till now, the folding mechanisms are still under extensive experimental and computational study. Structure-based modeling is one of the less costly computational methods. It has a simple formulated potential energy function summing over various geometrical restraints from one or more targeted structures. Here, we used a new all-atom structure-based method to investigate the folding mechanisms of GB1 and LB1. In this approach, folded structures of the two proteins were used to construct the restraints and they are stabilized by Lorentzian attractive term instead of conventional harmonic term.3 Our model is able to identify two-state and non-two-state proteins, and gives us more insights of the their folding pathways.1. Scalley, M. L., Yi, Q., Gu, H., McCormack, A., Yates, 3rd, J. R., and Baker, D. Biochemistry 36: 3373-82, 1997.2. McCallister, E., Alm, E., and Baker, D. Nat. Struct. Biol. 7: 669-673, 2000.3. Lee, J., Joo, K., Brooks, B., and Lee, J. J. Chem. Theory Comput. 11: 3211-3224, 2015.