Integral outer membrane proteins: structure assembly and function Flashcards
what are the functions of integral OMPs
- Transport of small molecules by uptake or efflux and secretion of macromolecules
- Catalysis
- structural (e.g binding of outer to peptidoglycan)
- Adhesion (receptors)
Explain the Beta barrel
- most integral outer membranes proteins for beta barrel
- A beta barrel is made from an antiparallel beta sheet which wraps around on itself to form a
closed barrel shape
-The outer ‘waist’ of the barrel is hydrophobic, so the protein stably integrates into the outer
membrane
Explain Porins
- Passive pore-forming OMPs
- Allow passage of low molecular weight solutes (salts, monosaccharides, antibiotics)
- Some selectivity towards charge (anions/cations) and substrate (eg sugars)
- 16 and 18 stranded beta barrels
- Some form trimers
- OmpF is a 16 stranded barrel and forms trimer
- Loop region folds down into lumen of barrel this regulates size of molecules passing in
- Charged residues in eyelet region regulate preference for anion or cations
Explain TonB-coupled Receptors
• Active, rather than passive transport
• Large family of transporters responsible for uptake of iron, heme and vitamin B
• Energy obtained from the proton motive force across the inner membrane through the
periplasmic protein TonB
• A 22-stranded beta barrel structure with a ‘plug’ domain which fills the barrel lumen
- Binding of TonB induces BtuB plug of transport cobalamin in E.coli
Explain secretion by FhaC
• FhaC is a member of a large family of OMPs (Omp85) which promote secretion and
insertion of proteins into the OM
• FhaC mediates the secretion of filamentous haemagluttinin (FHA)
• FhaC forms a 16-strand β-barrel structure
• the lumen of the barrel is occluded by a 20 residue α-helix and a large extracellular loop
(L6) which is essential for substrate secretion
• Polypeptide Transport-Associated, or POTRA domains, are α/β modules which extend
into the periplasm and bind substrates to assist translocation
- possible mechanism involves displacement of L6 and threading the nascent unfolded polypeptide chain through the barrel
Explain catalysis models
- Few few enzymes known to be integral OMPs
• Two examples are:
OmpT protease
phospholipase
Explain structural models
• Harder functional category to define, but there is evidence that several OMPs interact
directly with peptidoglycan, possibly helping to stabilize the OM relative to the
peptidoglycan layer.
• An example is the E coli protein OmpA
Explain Secretion models
- More complex OMPs associated with secretion
• Not all are transmembrane beta barrels
• Not all well characterised at the structural level
What are secretins
- Multidomain integral OMPs
• Involved in type II, type III secretion and type IV pilus biogenesis
• Form large oligomers and mediate passage of pili or protein complexes (eg cholera
toxin) across the OM
Explain adhesion with the example Opa-CEACAM
Opacity, or Opa proteins, are 8-stranded beta barrel OMPs from Neisseria meningitidis
- They bind to CarcinoEmbryonic Antigen-related Cell Adhesion Molecules (CEACAMs)
- CEACAMs are glycoproteins displayed on the surface of mucosal epithelial cells
- CEACAM recognition is thought to assist in colonization of mucosa
How are OMP formed
• Folding and insertion of OMPs into the OM is promoted by the Bam complex
• There are five Bam proteins, BamA to BamE
• BamA is related in sequence to FhaC and may work in a similar way
• Refolding is also assisted by DegP, which forms a large cage-like structure to support
OMP refolding
Medical relevance of OMP
• Some porins exhibit sequence hypervariability in their surface-exposed loops (example,
PorA from Neisseria meningitidis)
• Sequence variance can be used for typing bacteria
• PorA variability is caused by host immune selection pressure
• PorA has also been shown to act as a major protective antigen in meningitis vaccines
based on outer membrane vesicles
• Other porins have been shown to modulate antibiotic resistance, through mutations to
residues lining the pore
