Integral Membrane Proteins: Videos & Practice Problems

Integral membrane proteins are embedded in lipid bilayers, with alpha helices as the predominant secondary structure. They require detergents for isolation due to their strong membrane association. Transmembrane spanning domains, often formed by alpha helices, connect via loops. An exception is porins, which feature beta barrel motifs, allowing specific polar molecules to pass through membranes. These motifs consist of anti-parallel beta sheets, creating a hydrophilic interior and hydrophobic exterior, commonly found in bacterial membranes, mitochondria, and chloroplasts, reflecting their evolutionary origins.

Integral Membrane Proteins

In this video, we're going to talk in even more detail about integral membrane proteins. Recall that we already introduced integral membrane proteins in our previous lesson videos. We know that integral membrane proteins are integrated into the membrane, as shown below, and these are membrane-embedded proteins. Because integral membrane proteins are firmly anchored to the membrane, they are tightly associated with it, forming many interactions. To isolate an integral membrane protein from the membrane, we would first have to disrupt the membrane's structure using a detergent, and then we could isolate the protein. This shows how tightly associated these proteins are with the membrane.

The hydrophobic environment within the membranes actually stabilizes alpha helix structures. The alpha helix is the most prevalent secondary structure in integral membrane proteins. Most often, an integral membrane protein will contain an alpha helix structure. Looking at our image on the left, notice the integral membrane proteins, glycophorin on the left, and rhodopsin on the right, both form many alpha helix structures within the hydrophobic environment, stabilizing the alpha helix structure.

Integral membrane proteins contain at least one transmembrane spanning domain, which generally includes an alpha helix structure. For instance, glycophoran has one alpha helix and therefore one transmembrane spanning domain. Rhodopsin, on the right, has a total of seven alpha helices, each representing a transmembrane spanning domain. Multiple transmembrane spanning domains are typically connected by loops at the membrane surface, as seen in the loops connecting the alpha helices here.

In polar aqueous environments, proteins will fold such that the polar amino acids are on the perimeter to interact with the aqueous environment, while the non-polar amino acids fold into the interior of the protein due to their hydrophobic nature. However, in a hydrophobic environment within a membrane, the protein folds oppositely: the non-polar amino acids are on the perimeter and the polar amino acids are on the interior. This folding occurs within the hydrophobic environment inside the membrane, which is crucial for protein stability.

This concludes our introduction to integral membrane proteins. In our next lesson video, we will introduce a very specific integral membrane protein. See you there.

Integral Membrane Proteins

So in our last lesson video, we said that the alpha helix is the most common secondary structure in integral membrane proteins. But in this video, we're going to talk about an exception, which is in the integral membrane proteins called porins, which have beta barrel motifs. And so as we just mentioned, porins are just a class of integral membrane proteins that contain a beta barrel motif. And so recall from way back in our previous lesson videos that a motif is just a pattern or a combination of secondary protein structures. And so, as the name implies, porins function as pores or channels to allow specific molecules to cross the membrane.

Now, this beta barrel motif is really just a combination of anti-parallel beta sheets that come together to form a hollow cylinder, and this hollow cylinder has a hydrophilic interior and a hydrophobic exterior, and this specific pattern allows the passage of specific polar molecules to cross the membrane. And so, what's important to note is that these porins are commonly found in bacterial cell membranes, as well as in the membranes of mitochondria and chloroplasts. And so, really, this is not a surprise since we know the endosymbiotic theory suggests that mitochondria and chloroplasts used to be their own bacteria, and so again, not really a surprise that the bacteria, mitochondria, and chloroplasts all share this porin integral membrane protein in common.

And so if we take a look at our image down below, notice on the far left, we're showing you the Beta Barrel motif, which is again, just a combination of anti-parallel beta sheets that form this hollow cylinder. And again, the hollow cylinder has a hydrophilic interior and a hydrophobic exterior. And so when it's embedded in the membrane as we see here, the hydrophobic exterior is able to interact with the hydrophobic membrane. And then of course, the hydrophilic interior allows the passage of specific polar molecules to cross the membrane. And again, over here on the far right, we're just reminding you that these porins are commonly found in the membranes of both mitochondria and chloroplasts, as well as in bacteria. But of course, the mitochondria are going to be more relevant to us.

This here concludes our introduction to porins and beta barrel motifs, and again this is an exception to integral membrane proteins. And we'll be able to get some practice applying the concepts that we've learned in our next couple of videos. So I'll see you guys there.

Which of the following statements about integral proteins is NOT correct? 
a) They are firmly associated with the membrane. 
b) They contain hydrophobic regions that interact with hydrophobic lipid tails. 
c) They can be easily extracted/separated from lipid membranes by just a relatively small change in the pH. 
d) They commonly contain α-helices or multi-stranded β-barrels.

• A. They are firmly associated with the membrane.
• B. They contain hydrophobic regions that interact with hydrophobic lipid tails.
• C. They can be easily extracted/separated from lipid membranes by just a relatively small change in the pH.
• D. They commonly contain α-helices or multi-stranded β-barrels.

Answer: (C)

Integral membrane proteins are proteins that: 
a) Loosely associate with the membrane. 
b) Can be released from the membrane by slightly changing the pH. 
c) Can be released from the membrane by slightly changing the ionic strength of the solution. 
d) Penetrate or span the membrane.

• A. Loosely associate with the membrane.
• B. Can be released from the membrane by slightly changing the pH.
• C. Can be released from the membrane by slightly changing the ionic strength of the solution.
• D. Penetrate or span the membrane.

Answer: (D)

In the hydrophobic environment of a membrane, the α-helix of a protein folds such that the outer surfaces contain mostly _________________ amino acids, while _________________ amino acids are mostly buried on the inside. 
a) Non-polar; Hydrophobic. 
b) Polar; Hydrophilic. 
c) Hydrophobic; Non-polar. 
d) Polar; Hydrophobic. 
e) Non-polar; Hydrophilic.

• A. Non-polar; Hydrophobic.
• B. Polar; Hydrophilic.
• C. Hydrophobic; Non-polar.
• D. Polar; Hydrophobic.
• E. Non-polar; Hydrophilic.

Answer: (E)

Here’s what students ask on this topic:

What are integral membrane proteins and how are they associated with the membrane?

Integral membrane proteins are proteins embedded within the lipid bilayer of cell membranes. They are firmly anchored to the membrane due to their hydrophobic interactions with the lipid bilayer. These proteins often span the entire membrane, with regions exposed on both sides. To isolate them, detergents are required to disrupt the membrane structure. Integral membrane proteins typically contain alpha helices as their secondary structure, which are stabilized by the hydrophobic environment of the membrane.

What is the most common secondary structure found in integral membrane proteins?

The most common secondary structure found in integral membrane proteins is the alpha helix. The hydrophobic environment within the membrane stabilizes these alpha helices, making them prevalent in these proteins. For example, proteins like glycophorin and rhodopsin contain multiple alpha helices that span the membrane, forming transmembrane domains. These alpha helices are crucial for the protein's integration and function within the lipid bilayer.

How do porins differ from other integral membrane proteins?

Porins are a class of integral membrane proteins that differ from others by having a beta barrel motif instead of alpha helices. This beta barrel is formed by anti-parallel beta sheets that create a hollow cylinder with a hydrophilic interior and a hydrophobic exterior. This structure allows specific polar molecules to pass through the membrane. Porins are commonly found in bacterial cell membranes, as well as in the membranes of mitochondria and chloroplasts, reflecting their evolutionary origins.

Why are detergents necessary for isolating integral membrane proteins?

Detergents are necessary for isolating integral membrane proteins because these proteins are tightly associated with the lipid bilayer. The hydrophobic interactions between the protein and the membrane make them difficult to extract without disrupting the membrane structure. Detergents can solubilize the lipid bilayer, allowing the integral membrane proteins to be isolated without losing their functional properties. This process is essential for studying the structure and function of these proteins in detail.

What role do transmembrane spanning domains play in integral membrane proteins?

Transmembrane spanning domains are crucial for the function and integration of integral membrane proteins within the lipid bilayer. These domains, often formed by alpha helices, span the entire membrane, allowing the protein to interact with both the intracellular and extracellular environments. They are connected by loops at the membrane surface, facilitating the protein's structural stability and functional interactions. The number and arrangement of these domains can vary, influencing the protein's specific role in cellular processes.