Function
Porin or Outer Membrane Proteins (Omps) act as channels which allow passive diffusion of sugars, ions and amino acids. They are beta barrel proteins which traverse the cell membrane. In E. coli they are named according to their genes: C, F, G, etc. (OmpC, OmpF, OmpG).
Voltage-Dependent Anion Channel (VDAC) are ion channel Omps found in outer mitochondrial membrane[1]. In Pseudomonas aeruginosa the porin gene products are named OprD, OprE, OprK, OprP, etc. and OpdC, OpdH, etc.
Maltoporin (LamB) facilitates the diffusion of maltodextrin across the membrane[2].
See more details in
Voltage-Dependent Anion Channel (VDAC) is ion channel Omp found in outer mitochondrial membrane. In Pseudomonas aeruginosa the porin gene products are named OprD, OprK, OprP. The images at the left and at the right correspond to one representative porin structure, i.e. crystal structure osmoporin OmpC from Escherichia coli (2j1n). OmpC has three beta-barrels associated to form a tight trimer [3]. Porin is a transmembrane protein, as can be
seen from the hydrophobic ring around the protein, this makes it possible to submerge in the lipid bilayer (hydrophobic amino acids are sandybrown, hydrophilic ones are cyan). As you can see the hole in the protein is made of mainly hydrophilic chains thus making it possible for the sugar to pass through (these scenes were created by Nádori Gergely).
Gating and conduction of nano-channel forming proteins, a computational approach
The functional units of the living systems are cells whose internal physico-chemical conditions needed for optimum function are different from that of the external medium and are maintained by hydrophobic membrane barrier and reconstituted water filled nano-pore forming proteins. The structure of these channels dictates their function to some extent and makes them to open or close in response to various conditions in the surrounding medium including pH, temperature, ionic strength, potential difference, osmotic pressure, presence of certain ligands and so on. Due to very complex and sensitive structures of these molecules to the medium and the effect of their native location, lipid Bilayer, different from soluble proteins, the molecular structure of most of membrane proteins have not been worked out at atomic level yet. The discovery of the crystal structure of certain membrane macromolecules have paved the way to understand the mechanism(s) by which they control the traffic of certain molecules through the membrane and the way they respond to the internal and external stimulus and signal transduction.
In this study, certain nano-channel forming proteins, OmpF, OmpA, alpha-hemolysin and TolC whose structure is known at atomic level were considered to work out the relationship between their molecular structure and regional and overall dynamics[4]. The coordinates of all constituent atoms of the molecules, gathered from x-ray diffraction of molecule 3D crystal were obtained from Protein Data Bank (PDB) and used for calculation and simulation required for biophysical approaches. The extent of motion of different parts of the molecules inferred from Root-Mean-Square Deviation (RMSD) of a number of crystallized molecule whose averaged orientation represent the coordinate of different group is reported as B-factor of the protein in PDB.
Here, we used the molecular structure of the biomolecules with known 3D structure at atomic level as well as the B-factor to work out regional and global dynamics through theoretical and computational approaches in nonzero slowest modes of vibration. Based on equipartition theorem a criterion was defined to measure the extent of motion in exposed loops and turns on extracellular and cytosolic parts of the membrane channels as well as their channel forming parts acting as a membrane gate and extended along the hydrophobic core of the membrane.
The results obtained here were consistent with both experimental data obtained from voltage clamp studies of the reconstituted single channel in planner bilayer as well as theoretical approaches based on Molecular Dynamics (MD) and HOLE programs that show the molecular motions and the geometry of the channel lumen respectively. We noticed large motions in the intramembrane beta-barrel channel forming domains in TolC and alpha-hemolysin that possess large extracellular loops. However, there was less motion identified in the channel forming intramembrane parts of OmpF and OmpA, and the major motion recognized in the external loops.
Furthermore, we noticed that there is a conducting path (mini-channel) located between the L3 loop and the channel barrel wall (mini-channel) located between the L3 loop and the channel barrel wall that is in contact with membrane core. This path is different than the main known conducting path of the channel that is partially constricted by L3 loop. The conduction of the mini-channel is mainly governed by the flexibility of the L3 loop as well as the adjacent barrel wall. Thus, it might represent the effects of lateral pressure of the membrane on the channel conductivity.
The approach and algorithm used here requires less CPU power and time than MD, and makes it possible to conduct molecular studies of large molecules with known atomic structure at shorter time.
- ↑ Shoshan-Barmatz V, Israelson A, Brdiczka D, Sheu SS. The voltage-dependent anion channel (VDAC): function in intracellular signalling, cell life and cell death. Curr Pharm Des. 2006;12(18):2249-70. PMID:16787253
- ↑ Van Gelder P, Dumas F, Bartoldus I, Saint N, Prilipov A, Winterhalter M, Wang Y, Philippsen A, Rosenbusch JP, Schirmer T. Sugar transport through maltoporin of Escherichia coli: role of the greasy slide. J Bacteriol. 2002 Jun;184(11):2994-9. PMID:12003940
- ↑ Basle A, Rummel G, Storici P, Rosenbusch JP, Schirmer T. Crystal structure of osmoporin OmpC from E. coli at 2.0 A. J Mol Biol. 2006 Oct 6;362(5):933-42. Epub 2006 Aug 3. PMID:16949612 doi:10.1016/j.jmb.2006.08.002
- ↑ Besya AB, Mobasheri H, Ejtehadi MR. Gating and conduction of nano-channel forming proteins: a computational approach. J Biomol Struct Dyn. 2012 Aug 28. PMID:22928968 doi:10.1080/07391102.2012.712460
