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Topic: The position of positive and negative amino acids in a transmembrane helix  (Read 10249 times)

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Offline Babcock_Hall

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Re: The position of positive and negative amino acids in a transmembrane helix
« Reply #15 on: January 28, 2013, 04:49:45 PM »
Here is a link to a cartoon of glycophorin:
http://upload.wikimedia.org/wikipedia/commons/e/e9/Ch3f33.jpg

Offline Yggdrasil

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Re: The position of positive and negative amino acids in a transmembrane helix
« Reply #16 on: January 28, 2013, 10:55:20 PM »
I'm still not sure what the question is asking with regard to inside vs outside (whether this is referring to inside the membrane (i.e. the center of the bilayer) vs outside the membrane/near the edges of the bilayer or to extracellular vs intracellular/cytoplasmic).  However, here is useful information for both aspects:

Effects of amino acids as a function of their position in the bilayer:

Here is a useful figure from Hessa et al. 2007 giving exactly this information:

The graphs show the effects of each amino acid at each position along a TM helix on the insertion probability of the transmembrane helix (reported as a ΔG value, negative values mean more favorable insertion into the membrane).  The blue curve represents values measured by their experiments (see the paper as well as Hessa et al. 2005 for more information about how they measured the values).  The red curve represents values calculated from the observed position of amino acids from known membrane proteins structures.

Charged residues in extracellular vs intracellular loops:
There is a rule known as the "positive-inside" rule that determines the orientation of membrane proteins, first described by von Heijne in the 1980s.  He observed that cytoplasmic regions of membrane proteins were enriched in positively-charged residues while the extracellular regions of these proteins were deficient in these residues.  Furthermore, in a landmark paper in 1989, he demonstrated that by altering the distribution of these residues in a membrane protein, you could flip the topology of a membrane protein such that the cytoplasmic regions were now outside of the cell and the extracellular regions were now inside the cell!  AFAIK, the molecular basis for the "positive inside" rule is not well understood, but it may have something to do with how the Sec translocon, the protein that inserts TM helices into the membrane, reads amino acid sequences as they come off of the ribosome.

diksha

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Re: The position of positive and negative amino acids in a transmembrane helix
« Reply #17 on: January 30, 2013, 04:50:22 AM »
yeah charged amino acid side chains are hydrophilic

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