Peripheral Membrane Proteins: Study with Video Lessons, Practice Problems & Examples

Peripheral membrane proteins are located on the lipid bilayer's periphery, unlike integral membrane proteins that are embedded. They associate loosely with the membrane through electrostatic interactions and hydrogen bonding, making them easier to remove. These proteins can interact directly with phospholipid head groups or indirectly with integral proteins. Amphitropic proteins can exist both in the cytosol and associated with the membrane, highlighting their dynamic nature. Understanding these interactions is crucial for grasping membrane structure and function in biological systems.

Peripheral Membrane Proteins

In this video, we're going to talk more about peripheral membrane proteins. Recall in our previous lesson videos, we already introduced peripheral membrane proteins. We know that peripheral membrane proteins are found on the periphery or on the perimeter of the lipid bilayer. If you take a look at our image below, notice that all of these blue proteins that you see here are the peripheral membrane proteins. One thing to note is that the peripheral membrane proteins are only on the perimeter of the membrane and they are not integrated into the membrane like integral membrane proteins are. This purple one you see is an integral membrane protein.

Unlike integral membrane proteins which are integrated and tightly associated with the membrane, peripheral membrane proteins are only loosely associated with the membrane. This means that it's much easier to remove these peripheral membrane proteins from the membrane, and slight changes like changes in pH or changes in the ionic strength of a solution can remove these peripheral proteins from the membrane. These peripheral membrane proteins can associate with the membrane on either side. So, you can find them on both the extracellular side of the membrane or on the intracellular side of the membrane. Unlike integral membrane proteins, peripheral membrane proteins are going to associate with the membrane via electrostatic interactions and hydrogen bonding. These are the main interactions that allow peripheral membrane proteins to associate with the membrane.

This is different from the integral membrane proteins because the integral membrane proteins mostly associate with the membrane through hydrophobic interactions with the other fatty acid chains. But the peripheral membrane proteins, because they don't interact with the fatty acid chains, do not form hydrophobic interactions. They form electrostatic or hydrogen bonding interactions. Another important thing to note is that these peripheral membrane proteins can either associate directly with the membrane through interacting with the polar head groups of phospholipids or can interact indirectly with the membrane through interacting with the exposed surfaces of integral proteins. Notice that this peripheral membrane protein is interacting directly with the phospholipid heads forming electrostatic interactions and hydrogen bonding. However, this peripheral protein right here is not really interacting with the phospholipid heads. Instead, it's associated with the membrane because it's interacting with the exposed surface here of this integral membrane protein.

The last idea I want to leave you with is this idea of amphitropic proteins. This is a very specific type of peripheral membrane protein that can also be found diffused in the cytosol, which is the liquid found on the intracellular side of the membrane. You can see here that this particular peripheral membrane protein is associated with the intracellular side of the membrane and interacting with these phospholipids. But you'll also notice that this peripheral membrane protein has the ability to dissociate from the membrane and become dissolved or diffused in the cytosol. Amphitropic proteins can be found both associated with the membrane and dissolved in the cytosol. This concludes our lesson on peripheral membrane proteins, and we'll be able to apply the concepts that we've learned in our next couple of videos. I'll see you guys there.

Peripheral membrane proteins: 

a) Penetrate deeply into the lipid bilayer. 

b) Can only be released from membranes by disrupting membrane structure via treatment with detergents. 

c) Are non-covalently bound to membrane lipids or integral proteins. 

d) Consist of β-barrels forming a hollow cylinder that creates a pore within the membrane. 

e) Are covalently attached to carbohydrates that span the bilayer.

• A. Penetrate deeply into the lipid bilayer.
• B. Can only be released from membranes by disrupting membrane structure via treatment with detergents.
• C. Are non-covalently bound to membrane lipids or integral proteins.
• D. Consist of β-barrels forming a hollow cylinder that creates a pore within the membrane.
• E. Are covalently attached to carbohydrates that span the bilayer.

Label each of the following as a characteristic of (A) Integral and/or (B) Peripheral Membrane Proteins: 

a) Could function on either side of the membrane: ___________. 

b) Can act as a tunnel through the cell membrane: ___________. 

c) Attaches only at the surface of a cell's membrane: ___________. 

d) Extends through all or part of the membrane: ___________. 

e) Loosely associated with the membrane: ___________. 

f) Can act as amphitropic proteins: ___________.

So this practice problem wants us to label each of the following down below as either a characteristic of A, integral membrane proteins, and or B, peripheral membrane proteins. And so what can be helpful here is for us to draw a sketch of integral and peripheral membrane proteins. And so when we do that, we could get something that looks something like this, where you can see we have our phospholipid bilayer right here. And then, of course, the integral membrane protein is this one right here, spanning the entire membrane. And then the peripheral membrane protein is down over here on the perimeter. Now looking at part A, it says could function on either side of the membrane, and of course, this is referring to either functioning on the extracellular side of the membrane or functioning on the intracellular side of the membrane. It turns out that both, A, integral membrane proteins, and, B, peripheral membrane proteins can function on either side of the membrane. This is because integral membrane proteins can have an extracellular region like this one that could function on the outside of the cell and the integral membrane protein could also have an intracellular region that could function on the inside of the cell. And so, integral membrane proteins can function on either side. And the same goes for peripheral membrane proteins because they could either be associated with the intracellular side, but they could very well easily be on the extracellular side as well. And so, both, A and B, could function on either side of the membrane. Now, moving on to part B, it says, can act as a tunnel through the cell's membrane. Now, of course, because peripheral membrane proteins are only on the perimeter or the periphery, they can't really act as a tunnel to allow things to cross the membrane. Instead, the integral membrane proteins are perfect for this because they span the membrane and create a tunnel allowing molecules to travel through the tunnel and get through the membrane. And so, part B here is only going to apply to integral membrane proteins only. Part C says attaches only at the surface of a cell's membrane. And of course, we know that this is going to apply to peripheral membrane proteins. Those are the ones that are only attached to the surface. And so we can go ahead and put B here for peripheral membrane proteins. Part D says extends through all or part of the membrane. And, of course, we can visually see here that this only applies to the integral membrane protein A here. Part E says loosely associated with the membrane. Recall from our previous lesson videos that integral membrane proteins because they are integrated into the membrane, they form lots and lots of hydrophobic interactions with all of these fatty acid side chains that are here. This allows them to be firmly anchored or tightly associated with the membrane. And so, it's really the peripheral membrane proteins that are on the perimeter that are going to be the ones that are loosely associated with the membrane. And so this only applies to B, the peripheral membrane proteins. Last but not least, Part F says can act as amphitropic proteins. Recall from our last lesson video that amphitropic proteins are proteins that can both be associated with the membrane, but also reversibly bind to the membrane and act as proteins that are dissolved in the cytosol. And so this is only going to apply to peripheral membrane proteins. The ability to associate with the membrane and dissociate from the membrane can only apply to something that is loosely associated with the membrane. Integral membrane proteins would have a really hard time separating from the membrane and acting as a dissolved cytosolic protein. And so again, this is only going to apply to peripheral membrane proteins. And so this here concludes our practice problem, and I'll see you guys in our next video.

Here’s what students ask on this topic:

What are peripheral membrane proteins and how do they differ from integral membrane proteins?

Peripheral membrane proteins are proteins located on the periphery of the lipid bilayer, unlike integral membrane proteins that are embedded within the membrane. Peripheral membrane proteins associate loosely with the membrane through electrostatic interactions and hydrogen bonding, making them easier to remove. In contrast, integral membrane proteins are tightly associated with the membrane through hydrophobic interactions with the fatty acid chains of the lipid bilayer. Peripheral membrane proteins can interact directly with the polar head groups of phospholipids or indirectly with integral proteins, whereas integral membrane proteins span the membrane and are involved in various cellular functions such as transport and signaling.

How are peripheral membrane proteins removed from the membrane?

Peripheral membrane proteins can be removed from the membrane relatively easily due to their loose association. Changes in pH or ionic strength of the surrounding solution can disrupt the electrostatic interactions and hydrogen bonding that hold these proteins to the membrane. This is in contrast to integral membrane proteins, which require more drastic measures, such as the use of detergents, to be removed due to their strong hydrophobic interactions with the lipid bilayer.

What are amphitropic proteins and what is their significance?

Amphitropic proteins are a specific type of peripheral membrane protein that can exist both associated with the membrane and dissolved in the cytosol. These proteins can interact with the intracellular side of the membrane and then dissociate to diffuse in the cytosol. This dynamic nature allows amphitropic proteins to participate in various cellular processes, such as signaling and regulation, by moving between the membrane and the cytosol as needed. Understanding amphitropic proteins is crucial for grasping the flexibility and functionality of cellular membranes.

What types of interactions allow peripheral membrane proteins to associate with the membrane?

Peripheral membrane proteins associate with the membrane primarily through electrostatic interactions and hydrogen bonding. These interactions occur between the proteins and the polar head groups of phospholipids or the exposed surfaces of integral membrane proteins. Unlike integral membrane proteins, which interact with the hydrophobic fatty acid chains of the lipid bilayer, peripheral membrane proteins do not form hydrophobic interactions, making their association with the membrane less stable and easier to disrupt.

Can peripheral membrane proteins interact with both sides of the membrane?

Yes, peripheral membrane proteins can interact with both the extracellular and intracellular sides of the membrane. They can associate directly with the polar head groups of phospholipids or indirectly with the exposed surfaces of integral membrane proteins on either side of the lipid bilayer. This versatility allows peripheral membrane proteins to participate in various cellular processes, including signaling and structural support, on both sides of the membrane.