Jump to main content
Jump to site search

Issue 27, 2010
Previous Article Next Article

How does Proteinase 3 interact with lipid bilayers?

Author affiliations


Proteinase 3 (PR3) is a serine protease of the neutrophils whose membrane expression is relevant in a number of inflammatory pathologies. It has been shown to strongly interact with reconstituted bilayers containing dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG) or mixtures of both phospholipids. Here we present the results of molecular dynamics simulations of PR3 anchored at three different phospholipid bilayers: DMPC, DMPG and an equimolar mixture of DMPC/DMPG. We present for the first time a detailed model of membrane-bound PR3. A thorough inventory of the interaction between the lipids and the enzyme reveals three types of interactions contributing to the anchorage of PR3. Basic residues (R177, R186A, R186B, K187 and R222) interact via hydrogen bonds with the lipid headgroups to stabilize PR3 at the interfacial membrane region. Hydrophobic amino acids (V163, F165, F166, I217, L223, and F224) insert into the hydrophobic core below the carbonyl groups of the bilayers and six aromatic amino acids (F165, F192, F215, W218, F224, and F227) contribute electrostatic interaction via cation–π interactions with the choline groups of DMPC. PR3 presents all the characteristics of a peripheral membrane protein with an ability to bind negative phospholipids. Although the catalytic triad remains unperturbed by the presence of the membrane, the ligand binding sites are located in close proximity to the membrane and amino acids K99 and I217 interact significantly with the lipids. We expect the binding of long ligands to be modified by the presence of the lipids.

Graphical abstract: How does Proteinase 3 interact with lipid bilayers?

Back to tab navigation

Supplementary files

Publication details

The article was received on 17 Nov 2009, accepted on 11 May 2010 and first published on 09 Jun 2010

Article type: Paper
DOI: 10.1039/B924117E
Phys. Chem. Chem. Phys., 2010,12, 7487-7496

  •   Request permissions

    How does Proteinase 3 interact with lipid bilayers?

    T. Broemstrup and N. Reuter, Phys. Chem. Chem. Phys., 2010, 12, 7487
    DOI: 10.1039/B924117E

Search articles by author