2KDL
NMR structures of GA95 and GB95, two designed proteins with 95% sequence identity but different folds and functions
Summary for 2KDL
| Entry DOI | 10.2210/pdb2kdl/pdb |
| NMR Information | BMRB: 16116 |
| Descriptor | designed protein (1 entity in total) |
| Functional Keywords | evolution, folding, protein design, human serum albumin binding protein |
| Total number of polymer chains | 1 |
| Total formula weight | 6321.33 |
| Authors | He, Y.,Alexander, P.,Chen, Y.,Bryan, P.,Orban, J. (deposition date: 2009-01-12, release date: 2009-12-29, Last modification date: 2024-05-22) |
| Primary citation | Alexander, P.A.,He, Y.,Chen, Y.,Orban, J.,Bryan, P.N. A minimal sequence code for switching protein structure and function. Proc.Natl.Acad.Sci.USA, 106:21149-21154, 2009 Cited by PubMed Abstract: We present here a structural and mechanistic description of how a protein changes its fold and function, mutation by mutation. Our approach was to create 2 proteins that (i) are stably folded into 2 different folds, (ii) have 2 different functions, and (iii) are very similar in sequence. In this simplified sequence space we explore the mutational path from one fold to another. We show that an IgG-binding, 4beta+alpha fold can be transformed into an albumin-binding, 3-alpha fold via a mutational pathway in which neither function nor native structure is completely lost. The stabilities of all mutants along the pathway are evaluated, key high-resolution structures are determined by NMR, and an explanation of the switching mechanism is provided. We show that the conformational switch from 4beta+alpha to 3-alpha structure can occur via a single amino acid substitution. On one side of the switch point, the 4beta+alpha fold is >90% populated (pH 7.2, 20 degrees C). A single mutation switches the conformation to the 3-alpha fold, which is >90% populated (pH 7.2, 20 degrees C). We further show that a bifunctional protein exists at the switch point with affinity for both IgG and albumin. PubMed: 19923431DOI: 10.1073/pnas.0906408106 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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