the proteins pspa , im30 ( vipp1 ) , liah and yjfj belong to the pspa / im30 protein family . structurally , all family members are predicted to be mainly helical , and pspa , im30 and liah form high - molecular weight homo - oligomeric ring structures . solely yjfj is reported to not form such complexes , and , in fact , yjfj is the most distant and least studied protein in this family . the tendency of purified pspa , liah and im30 to form ring structures or other higher order oligomers is extremely pronounced and monomers represent a minor fraction in solution . the observed homo - oligomeric rings are strikingly similar : pspa has been calculated to form 36-mers , and liah also forms ring structures of that size range . im30 has the intrinsic propensity to form varying ring sizes containing ( at least ) 4868 monomers . nevertheless , besides a common phylogenic origin and obvious structural similarities , pspa , im30 and liah have different physiological functions . the phage shock protein ( psp ) system represents a conserved stress response system of bacteria and archaea . in enterobacteria , psp response proteins are encoded by the pspabcde operon and monocistronic pspf and pspg genes . thus far , the enterobacterial psp system is the best characterized representative involving a member of the pspa / im30 family . in the absence of stress one model suggests that the psp system is activated when pspa itself senses membrane defects or stress , resulting in liberation of pspf . as a result , transcription of the psp genes is enhanced and the pspa level increases , which triggers the formation of membrane - protecting pspa assemblies . in agreement with this hypothesis , alternatively , the main sensory role is attributed to the membrane components pspb and pspc . in this model , membrane stress results in recruitment of pspa to pspc , and a concomitant release of pspf activates the psp response . indeed , sensing of mistargeted secretins or membrane - destabilizing proteins requires pspb and pspc , which may function in conjunction with pspa . in non - enterobacteria , pspbc may be replaced by other sensory systems . recent analyses of the pspa - pspf interaction suggest that the pspaf complex does not necessarily need to dissociate to modulate psp gene expression . in summary , the function of pspa appears to be dual : ( i ) membrane binding and membrane protection as well as ( ii ) upregulation of corresponding genes . im30 ( inner membrane - associated protein of 30 kda ) , alternatively named vipp1 ( vesicle - inducing protein in plastids ) , is conserved in all organisms harboring thylakoid membranes ( tms ) , i.e. cyanobacteria ( except several prochlorococcus marinus strains ) , algae and higher plants . thus , while membrane binding and membrane protection appears to be conserved , im30 must have gained extra functions . although many im30-specific functions have been proposed in the past ( for a recent review , see ref . 21 ) , a recent report suggests that im30 can trigger membrane fusion upon membrane binding , a process crucial for tm biogenesis and maintenance . the lia system is highly conserved in bacillus and listeria species ( low gc gram - positive bacteria ) . its expression is controlled by the liafsr three - component system . in the absence of stress conditions , the bifunctional histidine kinase lias is kept in its phosphatase state by the inhibitor protein liaf , thereby repressing the activity of the transcriptional factor liar . under stress conditions , liaf presumably releases lias , which switches its activity from phosphatase to kinase state . once activated by phosphorylation liai is the membrane anchor of liah , which dynamically scans the membrane and recruits liah to the site of envelope damages . it is postulated that oligomeric liai / liah complexes stabilize a perturbed envelope at the sites of membrane damage . while all studied members of the pspa / im30 family have acquired specific functions during the course of evolution , pspa and im30 have been shown to directly bind to membrane surfaces and thereby to alter the structure and organization of membranes eventually resulting in membrane stabilization . liah is suggested to have the same activity , but experimental verification is still missing . pspa and im30 preferentially bind to negatively charged membranes or to surface curvature - stressed membranes . surface attachment of im30 or pspa increases the packing density of individual lipids , i.e. , the lipid bilayer becomes more ordered . increasing the lipid packing density might be a vital repair strategy if stress - induced defects occur in lipid bilayers . membrane stress resulting in membrane reorganization and eventually in membrane defects might be induced by heat or osmotic stress , by membrane remodeling agents , such as alcohols , as well as by external forces . importantly , the major lipid species of bacterial as well as tms are non - bilayer forming lipids ( such as pe ( phosphatidylethanolamine ) in e. coli and mgdg ( monogalactosyldiacylglycerol ) in cyanobacterial / chloroplasts ' tms ) . while mgdg is crucial for tm organization , excess of mgdg severely decreases the membrane stability . in fact , under prolonged stress affecting membrane integrity or fluidity , the mgdg content is adjusted . membrane binding of pspa or im30 proteins might therefore simply spatiotemporally stabilize short - living protein - free ( instable ) lipid patches by insertion of the hydrophobic side - chains of a membrane - binding amphipathic helix between the lipid acyl - chains of the cytoplasmic lipid bilayer leaflet . such membrane stabilizing mechanism is discussed for many membrane - active proteins or peptides that contain amphipathic helices , such as antimicrobial peptides or bar ( bin / amphiphysin / rvs)-domain proteins . in case of negative curvature stress or other defects in lipid bilayer structures , binding of pspa or im30 proteins to membrane surfaces might stabilize the bilayer structure by the discussed hydrophobic insertion mechanism . the ability of selected proteins to bind and to protect stressed membranes is important for the fitness and survival of microorganisms and plants , which are constantly exposed to different stresses , like cold , heat , reactive oxygen species ( generated , among other , by an intense photosynthetic activity ) , acid or organic solvents . membrane binding and protection has already been described for oligomeric proteins belonging to the small heat shock protein ( shsp ) family . shsps are low - molecular weight proteins ( 1542kda ) that form dynamic 9- to 50-mers . however , the shsps active unit is most certainly a dimer . hence , dimer formation requires dissociation of the oligomeric structure . under heat stress conditions , the cyanobacterial shsp hspa ( also named hsp17 ) delocalizes from the cytoplasm and binds to tms to protect the membrane ultrastructure by increasing the lipid order and reducing membrane fluidity . lo18 , a shsp from oenococcus oeni , forms 16-mer spherical complexes . under ethanol - induced membrane stress , furthermore , expression of the o. oeni lo18 in lactococcus lactis improved acid stress tolerance of l. lactis , and heterologous expression of hsp17 from caenorhabditis elegans enabled e. coli to grow at temperatures that are normally lethal for the wild - type strain . it is tempting to postulate a similar role for members of the pspa / im30 family , that is , that the oligomers dissociate on membrane surfaces upon membrane binding to stabilize defined membrane patches . in fact , for pspa and im30 dissociation of their large ring assemblies is indicated . im30 lmwo ( lower molecular weight oligomers ) bind with an about 5-fold higher affinity to pg liposomes than im30 rings , which argues for binding of monomers rather than high molecular mass oligomers to membrane surfaces and/or im30 ring disassembly upon membrane binding . increased membrane affinity of lmwo ( lower molecular weight oligomers ) im30 is discussed to originate from exposure of amphiphilic helices , which are otherwise involved in formation of coiled - coil - type interactions within im30 rings . since lmwo ( lower molecular weight oligomers ) appear to not be stable in solution , formation of the ring structures might simply be vital for shielding the amphiphilic helices . binding of an im30 ring to tms requires a free lipid area of about 380 nm ( total surface of the ring considered as a disc with an assumed ring diameter of 22 nm ) . in synechocystis pcc 6803 tms , the proportion of proteins ( weight / weight ) is 68% and in spinach tms , the proteins area occupancy has been estimated to be 75% . thus , binding of im30 rings seems barely probable in vivo within the crowded environment of a tm , unless stressed membrane areas are protein depleted or an unknown mechanism creates such large protein - free lipid domains . in fact , crowding is not homogeneous in cyanobacterial and plant tms that possess lateral heterogeneity with densely packed and more fluid areas . however , while a single im30 ring covers an area of 380 nm , the center of a ring is open leaving a free area of 80 nm . binding of smaller units ( such as monomers ) or flexibly rearranging scaffolds to damaged membranes could completely cover and protect damaged and/or stressed membranes by stabilizing the order of the lipid bilayer via filling the  gaps  between lipid head groups . functional characterization of pspa / im30 proteins has been notoriously difficult . but combining the lessons learned from its best studied members  the pspa from enterobacteria , im30 ( vipp1 ) from cyanobacteria and plants , and liah from firmicutes allowed extracting a first set of common features with respect to their oligomerization , membrane binding and putative membrane protecting function , as discussed here . we propose that membrane protection of members of the pspa / im30 protein family is mediated by ( 1 . ) binding of oligomeric / multimeric assemblies or ring structures to stressed membrane areas followed ( 2 . ) by ring dissociation , which results in exposure of membrane - binding amphiphilic helices and finally in coverage of a stressed membrane area by monomers or flexible scaffolds ( fig .  1 ) . notably , membrane attachment of oligomeric proteins and subsequent local disassembly results in a high monomer concentration that is confined to a selected membrane area . likely , membrane protection is mediated by binding of oligomeric / multimeric ( ring ) assemblies to stressed membrane area followed by ring dissociation and coverage of a stressed membrane area by monomers or flexible scaffolds . 
  pspa / im30 membrane binding and ring dissociation likely , membrane protection is mediated by binding of oligomeric / multimeric ( ring ) assemblies to stressed membrane area followed by ring dissociation and coverage of a stressed membrane area by monomers or flexible scaffolds . clearly , besides the proposed membrane - protective activity of pspa / im30 proteins , they have gained more specific functions in their special systems , and these activities are likely differently regulated . however , the here described insights can now serve as a starting point for more detailed functional and biochemical analyses that will ultimately unravel both general and organism - specific features of the ubiquitously distributed pspa / im30 protein family . this work was supported by the university of mainz ; and the ernst & margarete wagemann foundation .