2MJA

Solution Structure of Domain-Swapped GLPG

Summary for 2MJA

• Entry DOI: 10.2210/pdb2mja/pdb
• Related: 2LEP
• NMR Information: BMRB: 19713
• Descriptor: Rhomboid protease GlpG (1 entity in total)
• Functional Keywords: domain swapping, cell membrane, cytosol, membrane protein, micelles, serine protease, hydrolase, peptidase, rhomboid protease, intramembrane protease
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Multi-pass membrane protein (By similarity). Cell membrane; Multi-pass membrane protein (By similarity): E2QFS2
• Total number of polymer chains: 2
• Total formula weight: 15969.82

Authors

Ghasriani, H.,Kwok, J.KC.,Sherrat, A.R.,Goto, N.K. (deposition date: 2013-12-31, release date: 2014-11-12, Last modification date: 2024-05-15)

Primary citation

Ghasriani, H.,Kwok, J.K.,Sherratt, A.R.,Foo, A.C.,Qureshi, T.,Goto, N.K.
Micelle-Catalyzed Domain Swapping in the GlpG Rhomboid Protease Cytoplasmic Domain.
Biochemistry, 53:5907-5915, 2014

PubMed Abstract: Three-dimensional domain swapping is a mode of self-interaction that can give rise to altered functional states and has been identified as the trigger event in some protein deposition diseases, yet rates of interconversion between oligomeric states are usually slow, with the requirement for transient disruption of an extensive network of interactions giving rise to a large kinetic barrier. Here we demonstrate that the cytoplasmic domain of the Escherichia coli GlpG rhomboid protease undergoes slow dimerization via domain swapping and that micromolar concentrations of micelles can be used to enhance monomer-dimer exchange rates by more than 1000-fold. Detergents bearing a phosphocholine headgroup are shown to be true catalysts, with hexadecylphosphocholine reducing the 26 kcal/mol free energy barrier by >11 kcal/mol while preserving the 5 kcal/mol difference between monomer and dimer states. Catalysis involves the formation of a micelle-bound intermediate with a partially unfolded structure that is primed for domain swapping. Taken together, these results are the first to demonstrate true catalysis for domain swapping, by using micelles that work in a chaperonin-like fashion to unfold a kinetically trapped state and allow access to the domain-swapped form.

PubMed: 25162988
DOI: 10.1021/bi500919v

Experimental method

SOLUTION NMR