What Are Peripheral Proteins

Peripheral protein, or peripheral membrane proteins, are a group of biologically active molecules formed from amino acids which interact with the surface of the lipid bilayer of cell membranes. Unlike integral membrane proteins, peripheral proteins do not enter into the hydrophobic space within the cell membrane. Instead, peripheral proteins have specific sequences of amino acids which allow them to attract to the phosphate heads of the lipid molecules or to integral proteins.

The ability to attach to the membrane but not be locked to it allows peripheral proteins to work on the surface of the cell membrane. Peripheral proteins can be activated or disabled through a number of different pathways. Many peripheral proteins are also a part of many complex biochemical pathways. They can be involved in moving substances within or outside of a cell, activate other proteins and enzymes, or be involved in cell to cell interactions.

Structure of Peripheral Proteins

In the image below, several peripheral proteins are labeled. A peripheral protein does not have a definite structure, but it has several key aspects which make it a peripheral protein.

First, all peripheral proteins are associated with the cell membrane. The amino acid sequences of these proteins are unique in that they draw the proteins to the membrane, and they tend to congregate on the surface of the membrane. This allows them to be in the right place to carry out their designated action. In the image, the orange peripheral proteins are seen attached to either the phosphoglyceride lipid molecules which make up the lipid bilayer, or to integral proteins. A protein without these areas of amino acids would not be attracted to the membrane. It would be distributed evenly throughout the cytoplasm, and would not be a peripheral protein.

Second, peripheral proteins do not have a hydrophobic region of amino acids. This, and the polarity of other amino acid groups, keeps the peripheral proteins on the surface of the cell membrane. This is due to the amphipathic nature of phosphoglycerides. This means that the blue “head” region is polar and hydrophilic. The yellow “tails”, which constitute the middle of the membrane, are hydrophobic. To avoid being sucked into the membrane, peripheral proteins often have lots of hydrophilic amino acids exposed on their surface. Integral proteins expose hydrophobic amino acids in the middle, and hydrophilic amino acids on the parts exposed to water. This effectively locks them within the membrane.

Functions of Peripheral Proteins


One of the main roles of peripheral proteins is to direct and maintain both the intracellular cytoskeleton and components of the extracellular matrix. Both of these structures are formed by a series of organelles, filaments, and tubules. These small structures can provide rigidity or tension, but they need something to attach to.

Peripheral proteins can provide this point of attachment to the cell membrane. Cells use their cytoskeleton and extracellular matrix in many ways. Most often, they are used to control the shape and size of the cell. The cytoskeleton also provides functions of moving around products of the metabolism, and can be terminated or initiated from various peripheral proteins. For instance, a packet of proteins freshly packaged in the Golgi apparatus may move through the cytosol using the cytoskeleton. When it reaches the cell membrane to be expelled, specific peripheral proteins recognize the package, and start the process of expelling it.


The extracellular matrix, besides providing structural support, is also a vast network for gathering information in many cells. Bacteria, for instance, use a chain of reactions starting in the filaments of their extracellular matrix to stimulate peripheral proteins. These proteins then pass the message to integral proteins, and the message is carried inside the cell. Here it is passed to another peripheral protein, and eventually a response is initiated.

In this way, a microscopic organism or cell can learn much about its immediate environment. It is in this way that cells growing together to form a multicellular organism react and stop growing at the appropriate time. Peripheral proteins, as well as many other proteins and chemical signals, create chained reactions which can stimulate a response from the DNA or other organelles. In this way, a cell can grow more, react to a danger, or even release toxins of its own based on its microenvironment and the signals it receives.

In addition, many peripheral proteins can attach and detach from the membrane, based on certain factors such as pH and temperature. This allows a cell to develop different tactics for different environments, as well as control processes such as cell signaling and hormone reception.


Many peripheral proteins exist on the surface of cell membranes to carry out an action on a specific substrate. This may be to break it down or to combine it with another molecule. Peripheral proteins with simple enzyme functions are often peripheral proteins because the molecules they make are needed within or close to the cell membrane. For instance, several enzymes which control the synthesis and destruction of the cell membrane itself are peripheral proteins.

Molecule Transfer

Many peripheral proteins are also involved in transferring small molecules or electrons. These proteins, due to their affinity to the cell membrane, allow the reactions to stay in a tight space, and be highly coordinated. Many of the proteins found within the electron transport chain are peripheral proteins. These proteins transfer electrons from integral proteins they are attached to, and can pass the electrons to other proteins and molecules. Effectively, this stores the energy from the breakdown of the products of glycolysis into easily accessible molecules, or ATP. Other molecules, which are hydrophobic, can bind to peripheral proteins and be passed through various methods across or through the membrane.


1. Defensins are a type of molecule produced by the insect immune system. These peripheral proteins attach to the surface of bacterial cells, and create a small hole. This in turn breaks the cell open, allowing its contents to drain out, killing the bacteria. Why is it important that defensins are peripheral proteins?
A. It is not important
B. Peripheral proteins are attracted to cell membranes, where they work
C. The defensin proteins need to integrate into the membrane

2. Why do peripheral proteins have hydrophilic, rather than hydrophobic amino acids on their surface?
A. To form bonds with the hydrophilic region of the cell membrane
B. To lock itself with the membrane
C. To stop the molecule from detaching from the membrane

3. What is the main difference between and integral protein and a peripheral protein?
A. Integral proteins sit on the cell surface
B. Peripheral proteins cross the cell membrane
C. Integral proteins cross into the hydrophobic region of the membrane


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Nelson, D. L., & Cox, M. M. (2008). Principles of Biochemistry. New York: W.H. Freeman and Company.

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