Spanins and Holins

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HOW TO DEAL WITH SPANINS AND HOLINS

  • Jim is VERY VERY VERY keen that we don't obsolete the current holin terms. Becky volunteered from the 31st July jamboree to go away and look at the holin and spanin terms. Her suggestions are below.
  • Do we want the children of spanin terms? At the least, the defn for spanin in MeGO needs to be altered.
  • We may be able to put a process terms for spanin under 'disruption by symbiont of host cell (GO:0044004)' - Jane


HOLINS

Background to what holins do:

  • essential for host lysis by bacteriophage.
  • small membrane proteins
  • accumulate in membrane then act to permeabilize the membrane (by making themselves into a hole). Permealized either to an endolysin, so the endolysin can reach the cell wall and degrade it (thus the holin controls the functional access of the endolysin to the murein) or to ions to cause a collapse of the membrane potential.
  • Doesn't appear to be known if the hole is just a hole, or an actual channel.
  • Holins act as 'clocks' and only make the holes when the time is right. Not sure how this is judged yet.
  • If the holins are not considered to be channels (see question below), there's no suitable function term, short of 'hole activity'. Therefore, I propose to obsolete the existing 'holin activity' terms, and replace them with new process terms. We've tried obsoleting 'holin' twice before, but it's still managed to stay in the ontology with 'activity' bunged on the end... sneaky. Here's my suggestion... let me know if it works for you:
obsolete: 
holin activity ; GO:0034290
canonical holin activity ; GO:0034291
pinholin activity ; GO:0034292
Reason for obsoletion: These terms represent a family of proteins and not an activity. Replacement terms are suggested below.
Add new terms:
regulation of plasma membrane permeability ; GO:NEW1
negative regulation of plasma membrane permeability ; GO:NEW2
positive regulation of plasma membrane permeability ; GO:NEW3
plasma membrane permeabilization involved in cytolysis by virus of host cells ; GO:NEW4
plasma membrane permeabilization to endolysin involved in cytolysis by virus of host cells ; GO:NEW5
plasma membrane permeabilization to ions involved in cytolysis by virus of host cells ; GO:NEW6

Definitions of new terms:

regulation of plasma membrane permeability ; GO:NEW1
Any process that modulates the frequency, rate or extent of the passage or uptake of molecules by a plasma membrane.
is_a: regulation of biological quality ; GO:0065008
is_a: plasma membrane organization ; GO:0007009
(Similar for negative and positive children)
plasma membrane permeabilization involved in cytolysis by virus of host cells ; GO:NEW4
synonym: holin-mediated permeabilization [EXACT?]
synonym: holin-dependent membrane permeabilization [EXACT?]
synonym: positive regulation of plasma membrane permeability involved in cytolysis by symbiont of host cells [EXACT]
synonym: cytoplasmic hole formation during host lysis by bacteriophage [NARROW? or EXACT?]
synonym: holin activity [RELATED]
The temporally-regulated permeabilization of the host plasma membrane (cytoplasmic membrane) by a virus/bacteriophage during lysis of the host cell.
Comment: The transmembrane holin proteins accumulate in the membrane of the host cell, and at a specific time point form a hole through the cytoplasmic membrane  that allows the passage of enzymes and/or other molecules to lyse the host cell.
plasma membrane permeabilization to endolysin involved in cytolysis by virus of host cells ; GO:NEW5
The temporally-regulated permeabilization of the plasma membrane (cytoplasmic membrane) to a fully-folded phage-encoded endolysin (murein-degradase), so the  endolysin can reach and degrade the murein within the cell wall during lysis of the host cell by a virus.
exact synonym: endolysin-specific hole formation during host cell lysis by bacteriophage
synonym: canonical holin activity [RELATED]

plasma membrane permeabilization to ions involved in cytolysis by virus of host cells ; GO:NEW6
The temporally-regulated permeabilization of the plasma membrane (cytoplasmic membrane) to ions, causing irreversible depolarization of the cell membrane and lysis of the host cell by a virus [PMID 19861547].
synonym: hole formation during host cell lysis by bacteriophage [EXACT?]
synonym: pinholin activity [RELATED]


QUESTIONS ON HOLIN TERMS:

  • QUESTION 1: membrane organization is under 'cellular process'… this is going to cause problems again, isn't it.
  • QUESTION 2: wrt whether the synonyms should be exact or narrow, would you use these terms to annotate anything other than holins?
  • QUESTION 3: wrt definitions & synonyms, is this process specific to bacteriophages?
  • QUESTION 4: Am I right in saying that it's the plasma membrane (equivalent to the cytoplasmic/inner membrane in bacteria) that the holes are formed in?
  • QUESTION 5: Would you say that a holin should be annotated to 'channel activity'?

SPANINS

Background to what spanins do (PMID 20734329):

  • Acts at the 3rd step in lysis (acting after holins and endolysins): involved in disrupting the outer membrane (OM).
  • span the periplasm
  • form dimers and monomers
Add new terms:
disruption by virus of host cell outer membrane ; GO:NEW
disruption by virus of host cell outer membrane involved in cytolysis by virus of host cells ; GO:NEW 
New term definitions:
disruption by virus of host cell outer membrane ; GO:NEW
A process by which a virus has a negative effect on the functioning of the host's cell outer membrane. The cell outer membrane is a lipid bilayer that forms the  outermost layer of the cell envelope.
disruption by virus of host cell outer membrane involved in cytolysis by virus of host cells ; GO:NEW 
A process by which a virus has a negative effect on the functioning of the host's cell outer membrane that contributes to lysis of the host cell.
synonym: spanin activity [RELATED]
synonym: OM disruption during cell lysis [PMID: 20734329]
comment: Consider also annotating to 'host cell periplasmic space ; GO:0044229'


QUESTIONS ON SPANIN TERMS:

  • QUESTION: Do you know HOW the spanins disrupt the outer membrane? Is it just by being wedged in the periplasmic space? Might be by fusing the OM with the plasma membrane (PMID 20080651)