2K7V

Deletions in a surface loop divert the folding of a protein domain into a metastable dimeric form

Summary for 2K7V

• Entry DOI: 10.2210/pdb2k7v/pdb
• NMR Information: BMRB: 15931
• Descriptor: Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (1 entity in total)
• Functional Keywords: misfolded dimer, acyltransferase, glycolysis, lipoyl, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 17774.65

Authors

Stott, K.M.,Yusof, A.M.,Perham, R.N.,Jones, D.D. (deposition date: 2008-08-27, release date: 2009-09-15, Last modification date: 2024-05-08)

Primary citation

Stott, K.M.,Yusof, A.M.,Perham, R.N.,Jones, D.D.
A surface loop directs conformational switching of a lipoyl domain between a folded and a novel misfolded structure.
Structure, 17:1117-1127, 2009

PubMed Abstract: A prominent surface loop links the first two beta strands of the lipoyl domain (E2plip) from the pyruvate dehydrogenase multienzyme complex of Escherichia coli. We show here that shortening this loop by two residues generates a protein that populates two structurally distinct stable conformers: an active, native-like monomer (HM) and a functionally compromised misfolded dimer (LM). Conversion of LM to HM was observed after exposure to temperatures above 50 degrees C. Removal of two additional residues from the loop caused the protein to adopt exclusively the misfolded conformation. Detailed NMR structural studies of the misfolded dimer reveal that the N-terminal half of the domain was unfolded and dynamic, whereas the C-terminal halves of two monomers had associated to form a structure with two-fold symmetry and a topology mimicking that of the folded monomer. The surface loop is therefore a hitherto unsuspected determinant in the folding process that leads to a functional protein.

PubMed: 19679089
DOI: 10.1016/j.str.2009.07.001

Experimental method

SOLUTION NMR