TL;DR: In water, charged parts will tend to rotate outward. In neutrally charged hydrophobic environments, non-charged protein parts will try to face outward. Cell membrane is a partially-hydrophobic environment, so one of the standard protein-folding rules is inverted in its fatty-layer zone. When taken out of it, the protein may literally flip (and also clump, with both itself and other membrane proteins).
Trans-membrane (TM) proteins aren’t woven, they’re sewed (and then folded). They’re threaded in and out of the membrane through a pore, as the ribosome prints them. (While the sewing is loose, not tight, sewing is almost exactly the right way to think about it.*)
Amino acids (AA) can be charged +, charged -, or roughly neutral depending on sequence/peptide. AAs are the component parts of the thread that folds into proteins, and a long string of +charged AAs can help make a whole region on that thread charged (or for 0charge, neutral).
Water molecules are charged and bi-polar. Near a strong charge, they’ll rotate their faces like a magnet to put their + end near a -, or—end near a +. Alternatively phrased: charged molecules are usually hydrophilic and drawn to water molecules (more like water-molecules are drawn to them… but same difference), while large non-charged molecules (ex: the main-body of fats and oils) are hydrophobic by comparison and tend to clump among themselves (something weak Van der Waals forces something).
(You know how oil and water self-assort, and don’t mix? It’s a lot like that.)
The membrane is charged on the surfaces (both inner and outer surface)**, but has a fatty, hydrophobic, neutrally-charged environment in its middle.
This alters the preferred/stable protein structure for the AAs in the (fatty, hydrophobic) threading-zone. In water, charged parts will tend to rotate outward. In neutrally charged hydrophobic environments, non-charged protein parts will try to face outward. While the charged AAs will… wish they had anywhere else to be; usually gravitating harder towards any water they can find, or to each other.
So, one of the standard protein-folding rules is inverted in the fatty-layer zone. Basically.
If you took them out of the embedded fat layer, they would literally flip (to the extent to which that was physically allowed), or that section would clump with the uncharged middle-portions of itself or other TM proteins.***
And since a sizable fraction of TM proteins are cross-membrane pores (transporting a specific molecule from one side of the membrane to the other), getting that cross-membrane portion accurately matters a LOT if you’re trying to understand function.
* For once-through proteins, there’s even a specialized trans-membrane starter-peptide-sequence “needle” that can tell the cell it’s a TM protein in the first place. It’s the first thing to get threaded through, and gets cut off after its job is done. See: Signal Peptide.
** Membrane is a “lipid bi-layer” technically; it’s like a “charged-end—fat & fat—charged-end” sandwich
*** Side-note: TM proteins float around in the membrane like rafts. It’s pretty cool.
To give a somewhat-simplified explanation...
TL;DR: In water, charged parts will tend to rotate outward. In neutrally charged hydrophobic environments, non-charged protein parts will try to face outward. Cell membrane is a partially-hydrophobic environment, so one of the standard protein-folding rules is inverted in its fatty-layer zone. When taken out of it, the protein may literally flip (and also clump, with both itself and other membrane proteins).
Trans-membrane (TM) proteins aren’t woven, they’re sewed (and then folded). They’re threaded in and out of the membrane through a pore, as the ribosome prints them. (While the sewing is loose, not tight, sewing is almost exactly the right way to think about it.*)
Amino acids (AA) can be charged +, charged -, or roughly neutral depending on sequence/peptide. AAs are the component parts of the thread that folds into proteins, and a long string of +charged AAs can help make a whole region on that thread charged (or for 0charge, neutral).
Water molecules are charged and bi-polar. Near a strong charge, they’ll rotate their faces like a magnet to put their + end near a -, or—end near a +. Alternatively phrased: charged molecules are usually hydrophilic and drawn to water molecules (more like water-molecules are drawn to them… but same difference), while large non-charged molecules (ex: the main-body of fats and oils) are hydrophobic by comparison and tend to clump among themselves (something weak Van der Waals forces something).
(You know how oil and water self-assort, and don’t mix? It’s a lot like that.)
The membrane is charged on the surfaces (both inner and outer surface)**, but has a fatty, hydrophobic, neutrally-charged environment in its middle.
This alters the preferred/stable protein structure for the AAs in the (fatty, hydrophobic) threading-zone. In water, charged parts will tend to rotate outward. In neutrally charged hydrophobic environments, non-charged protein parts will try to face outward. While the charged AAs will… wish they had anywhere else to be; usually gravitating harder towards any water they can find, or to each other.
So, one of the standard protein-folding rules is inverted in the fatty-layer zone. Basically.
If you took them out of the embedded fat layer, they would literally flip (to the extent to which that was physically allowed), or that section would clump with the uncharged middle-portions of itself or other TM proteins.***
And since a sizable fraction of TM proteins are cross-membrane pores (transporting a specific molecule from one side of the membrane to the other), getting that cross-membrane portion accurately matters a LOT if you’re trying to understand function.
* For once-through proteins, there’s even a specialized trans-membrane starter-peptide-sequence “needle” that can tell the cell it’s a TM protein in the first place. It’s the first thing to get threaded through, and gets cut off after its job is done. See: Signal Peptide.
** Membrane is a “lipid bi-layer” technically; it’s like a “charged-end—fat & fat—charged-end” sandwich
*** Side-note: TM proteins float around in the membrane like rafts. It’s pretty cool.