Membrane bounded proteins and Functions

Definition:
A membrane protein is a protein molecule that is attached to, or associated with the
membrane of a cell or an organelle. More than half of all proteins interact with
membranes.
Membrane proteins are proteins that interact with biological membranes. They are one of the
common types of protein along with soluble globular proteins, fibrous proteins, and disordered
proteins.They are targets of over 50% of all modern medicinal drugs. It is estimated that 2030%
of all genes in most genomes encode membrane proteins. In addition to the lipid bilayer, the cell
membrane also contains a number of proteins.The lipid bilayer provides the structure for the cell
membrane, membrane proteins allow for many of the interactions that occur between cells.

Membrane proteins are easy to move with in the lipid bilayer as a result of its fluidity. Although
this is true for most proteins, they can also be confined to certain areas of the bilayer with
enzymes. Membrane proteins perform various functions, and this diversity is reflected in the
significantly different types of proteins associated with the lipid bilayer.
Functions of Membrane bounded Proteins:
Following are the functions of membrane proteins:
1. Structural proteins are attached to microfilaments in the cytoskeleton which ensures
stability of the cell.
2. Cell adhesion molecules allow cells to identify each other and interact. Such proteins are
involved in immune response.
3. Membrane enzymes produce a variety of substances essential for cell function.
4. Membrane receptor proteins serve as connection between the cell's internal and external
environments.

5. Transport proteins play an important role in the maintenance of concentrations of ions.

These transport proteins come in two forms: carrier proteins and channel proteins.

Types of membrane bounded proteins:

Following are three main types of membrane bounded proteins.
1. Integral membrane proteins.
2. Peripheral membrane proteins
3. Lipid-anchored proteins

1. Integral membrane proteins:

Integral membrane proteins are those which are permanently bound to the
lipid bilayer. These require a detergent (such as SDS or Triton X-100) or some other
apolar solvent to be displaced. An integral membrane protein (IMP) is a type of
membrane protein that is permanently attached to the biological membrane. All
transmembrane proteins are IMPs, but not all IMPs are transmembrane proteins.IMPs
comprise a significant fraction of the proteins encoded in an organism's genome.Proteins
that cross the membrane are surrounded by "annular" lipids (see annular lipid shell),
which are defined as lipids that are in direct contact with a membrane protein. Such
proteins can be separated from the biological membranes only using detergents, nonpolar
solvents, or sometimes denaturing agents.

There are three main categories of Integral membrane proteins.

(I)
Transmembrane proteins:
Transmembrane proteins, are proteins that are permanently attached to the lipid membrane and
span across the membrane (at least once). The transmembrane regions of the proteins are either
beta-barrels or alpha-helical. The alpha-helical domains are present in all types of biological
membranes including outer membranes. The beta-barrels were found only in outer membranes of
Gram-negative bacteria, lipid-rich cell walls of a few Gram-positive bacteria, and outer

membranes of mitochondria and chloroplasts. transmembrane proteins span from one side of a
membrane through to the other side of the membrane. Firm attachment of TP to biological
membrane is aided by a special class of membrane lipids, called annular lipid shell. Many TPs

function as gateways or "loading docks" to deny or permit the transport of specific substances
across the biological membrane, to get into the cell, or out of the cell as in the case of waste
byproducts. As a response to the shape of certain molecules these "freight handling" TPs may
have special ways of folding up or bending that will move a substance through the biological
membrane.Transmembrane proteins are polytopic proteins that aggregate and precipitate in
water.
(A) Rhodopsin:
Bacterial rhodopsins are a family of bacterial opsins. They are retinal-binding proteins
that provide light-dependent ion transport and sensory functions to a family of halophilic
and other bacteria. They are integral membrane proteins with seven transmembrane
helices, the last of which contains the attachment point for retinal (a conserved lysine).
Bacteriorhodopsin contains 7 transmembrane - helices. The purple membrane of
Halobacterium halobium contains ordered sheets of bacteriorhodopsin, a protein of 248
amino acids residues which binds retnal, the same photosensitve pigment that is used

to capture light in our eyes. Bacteriorhodopsin uses the energy of light to pump protons

across the membrane.

7 transmembrane - helices hooked together by loops.

(B) Porins
Porins are beta barrel proteins that cross a cellular membrane and act as a pore through
which molecules can diffuse. Unlike other membrane transport proteins, porins are large
enough to allow passive diffusion, i.e., they act as channels that are specific to different
types of molecules. They are present in the outer membrane of Gram-negative bacteria
and some Gram-positive bacteria. Porins typically control the diffusion of small
metabolites like sugars, ions, and amino acids. Porin channel are made up and down
barrels.

(II) Integral monotopic proteins:

Integral monotopic proteins are proteins that are permanently attached to the lipid
membrane from only one side and do not span across the membrane. Integral monotopic
proteins, are permanently attached to the membrane from one side.
Three-dimensional structures of the following integral monotopic proteins have been determined:

prostaglandin H2 syntheses 1 and 2 (cyclooxygenases)

lanosterol synthase and squalene-hopene cyclase

microsomal prostaglandin E synthase

carnitine O-palmitoyltransferase 2

There are also structures of integral monotopic domains of transmembrane proteins:

monoamine oxidases A and B

fatty acid amide hydrolase

mammalian cytochrome P450 oxidases

corticosteroid 11-beta-dehydrogenases

(2).Peripheral membrane proteins:

Peripheral membrane proteins are proteins that adhere only temporarily to the biological
membrane with which they are associated. These molecules attach to integral membrane
proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits
of many ion channels and transmembrane receptors, for example, may be defined as peripheral
membrane proteins. In contrast to integral membrane proteins, peripheral membrane proteins
tend to collect in the water-soluble component, or
fraction, of all the proteins extracted during a protein
purification procedure. Proteins with GPI anchors are
an exception to this rule and can have purification
properties similar to those of integral membrane
proteins.The reversible attachment of proteins to
biological membranes has shown to regulate cell
signaling and many other important cellular events,
through a variety of mechanisms. For example, the close association between many enzymes and
biological membranes may bring them into close proximity with their lipid substrate(s).

Membrane binding may also promote rearrangement, dissociation, or conformational changes

within many protein structural domains, resulting in an activation of their biological activity.
Additionally, the positioning of many proteins are localized to either the inner or outer surfaces
or leaflets of their resident membrane. This facilitates the assembly of multi-protein complexes
by increasing the probability of any appropriate proteinprotein interactions.

3 Lipid Anchored proteins:

Lipid-anchored proteins (also known as lipid-linked proteins) are proteins located on the surface
of the cell membrane that are covalently attached to lipids embedded within the cell membrane.
These lipids insert and assume a place in the bilayer structure of the membrane alongside the
similar fatty acid tails. The lipid-anchored protein can be located on either side of the cell
membrane.Thus, the lipid serves to anchor the protein to the cell membrane.The lipid groups
plays a role in protein interaction and can contribute to the function of the protein to which it is
attached. Furthermore, the lipid serves as a mediator of membrane associations or as a
determinant for specific protein-protein interactions. For example, lipid groups can play an
important role in increasing molecular hydrophobicity. This allows for the interaction of proteins
with cellular membranes and protein domains.Overall, there are three main types of lipidanchored proteins which include prenylated proteins, fatty acylated proteins and
glycosylphosphatidylinositol-linked proteins (GPI). A protein can have multiple lipid groups
covalently attached to it, but the site where the lipid binds to the protein depends both on the
lipid group and protein.