2MH8

GA-79-MBP cs-rosetta structures

Summary for 2MH8

• Entry DOI: 10.2210/pdb2mh8/pdb
• NMR Information: BMRB: 19623
• Descriptor: GA-79-MBP, maltose binding protein (1 entity in total)
• Functional Keywords: mbp, maltose binding protein, ga, human serum albumin binding protein, protein binding
• Biological source: Streptococcus dysgalactiae
• Total number of polymer chains: 1
• Total formula weight: 6312.25

Authors

He, Y.,Chen, Y.,Porter, L.,Bryan, P.,Orban, J. (deposition date: 2013-11-19, release date: 2015-04-08, Last modification date: 2024-05-01)

Primary citation

Porter, L.L.,He, Y.,Chen, Y.,Orban, J.,Bryan, P.N.
Subdomain interactions foster the design of two protein pairs with 80% sequence identity but different folds.
Biophys.J., 108:154-162, 2015

PubMed Abstract: Metamorphic proteins, including proteins with high levels of sequence identity but different folds, are exceptions to the long-standing rule-of-thumb that proteins with as little as 30% sequence identity adopt the same fold. Which topologies can be bridged by these highly identical sequences remains an open question. Here we bridge two 3-α-helix bundle proteins with two radically different folds. Using a straightforward approach, we engineered the sequences of one subdomain within maltose binding protein (MBP, α/β/α-sandwich) and another within outer surface protein A (OspA, β-sheet) to have high sequence identity (80 and 77%, respectively) with engineered variants of protein G (GA, 3-α-helix bundle). Circular dichroism and nuclear magnetic resonance spectra of all engineered variants demonstrate that they maintain their native conformations despite substantial sequence modification. Furthermore, the MBP variant (80% identical to GA) remained active. Thermodynamic analysis of numerous GA and MBP variants suggests that the key to our approach involved stabilizing the modified MBP and OspA subdomains via external interactions with neighboring substructures, indicating that subdomain interactions can stabilize alternative folds over a broad range of sequence variation. These findings suggest that it is possible to bridge one fold with many other topologies, which has implications for protein folding, evolution, and misfolding diseases.

PubMed: 25564862
DOI: 10.1016/j.bpj.2014.10.073

Experimental method

SOLUTION NMR