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Integral membrane protein

 

 
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Integral membrane protein
 
 
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An Integral Membrane Protein (IMP) is a protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 molecule
Molecule

In chemistry, a molecule is defined as a sufficiently stable, electric charge neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds....
 (or assembly of proteins) that is permanently attached to the biological membrane
Biological membrane

A biological membrane or biomembrane is an enclosing or separating amphipathic layer that acts as a barrier within or around a cell . It is, almost invariably, a lipid bilayer, composed of a double layer of lipid-class molecules, specifically phospholipids and cholesterol, with occasional integral membrane protein intertwined, some o...
. Such proteins can be separated from the biological membranes only using detergent
Detergent

A detergent is a material intended to assist cleaning. The term is sometimes used to differentiate between soap and other surfactants used for cleaning....
s, nonpolar solvents, or sometimes denaturing
Denaturation (biochemistry)

Denaturation is a process in which proteins or nucleic acids lose their structure by application of some external stress or compound for example, treatment of proteins with strong acids or bases, high concentrations of inorganic salts, organic compound solvents , or heat....
 agents.

IMPs comprise a very significant fraction of the proteins encoded in the genome
Genome

In classical genetics, the genome of a diploid organism including eukarya refers to a full set of chromosomes or genes in a gamete; thereby, a regular somatic cell contains two full sets of genomes....
.

e-dimensional structures of only ~160 different integral membrane proteins are currently determined at atomic resolution by X-ray crystallography
X-ray crystallography

X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and scatters into many different directions....
 or Nuclear magnetic resonance
Nuclear magnetic resonance

Nuclear magnetic resonance is the name given to a physical resonance phenomenon involving the observation of specific quantum mechanics magnetism properties of an atomic atomic nucleus in the presence of an applied, external magnetic field....
 spectroscopy
Spectroscopy

Spectroscopy was originally the study of the interaction between radiation and matter as a function of wavelength . In fact, historically, spectroscopy referred to the use of visible light dispersed according to its wavelength, e.g....
 due to the difficulties with extraction and crystallization.






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An Integral Membrane Protein (IMP) is a protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 molecule
Molecule

In chemistry, a molecule is defined as a sufficiently stable, electric charge neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds....
 (or assembly of proteins) that is permanently attached to the biological membrane
Biological membrane

A biological membrane or biomembrane is an enclosing or separating amphipathic layer that acts as a barrier within or around a cell . It is, almost invariably, a lipid bilayer, composed of a double layer of lipid-class molecules, specifically phospholipids and cholesterol, with occasional integral membrane protein intertwined, some o...
. Such proteins can be separated from the biological membranes only using detergent
Detergent

A detergent is a material intended to assist cleaning. The term is sometimes used to differentiate between soap and other surfactants used for cleaning....
s, nonpolar solvents, or sometimes denaturing
Denaturation (biochemistry)

Denaturation is a process in which proteins or nucleic acids lose their structure by application of some external stress or compound for example, treatment of proteins with strong acids or bases, high concentrations of inorganic salts, organic compound solvents , or heat....
 agents.

IMPs comprise a very significant fraction of the proteins encoded in the genome
Genome

In classical genetics, the genome of a diploid organism including eukarya refers to a full set of chromosomes or genes in a gamete; thereby, a regular somatic cell contains two full sets of genomes....
.

Structure

Three-dimensional structures of only ~160 different integral membrane proteins are currently determined at atomic resolution by X-ray crystallography
X-ray crystallography

X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and scatters into many different directions....
 or Nuclear magnetic resonance
Nuclear magnetic resonance

Nuclear magnetic resonance is the name given to a physical resonance phenomenon involving the observation of specific quantum mechanics magnetism properties of an atomic atomic nucleus in the presence of an applied, external magnetic field....
 spectroscopy
Spectroscopy

Spectroscopy was originally the study of the interaction between radiation and matter as a function of wavelength . In fact, historically, spectroscopy referred to the use of visible light dispersed according to its wavelength, e.g....
 due to the difficulties with extraction and crystallization. In addition, structures of many water-soluble domains of IMPs are available in the Protein Data Bank
Protein Data Bank

The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids. . The data, typically obtained by X-ray crystallography or Protein NMR and submitted by biologists and biochemistry from around the world, are released into the public domain, and can be accessed at no charge...
. Their membrane-anchoring a-helices have been removed to facilitate the extraction and crystallization.

IMPs can be divided into two groups:
  1. Transmembrane proteins
  2. Integral monotopic proteins
    Peripheral membrane protein

    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....
    .


Integral transmembrane protein

The most common type of IMP is the transmembrane protein
Transmembrane protein

A transmembrane protein is a protein that spans the entire biological membrane. Transmembrane proteins aggregate and precipitate in water. They require detergents or nonpolar solvents for extraction, although some of them can be also extracted using denaturing agents....
 (TM), which spans the entire biological membrane
Biological membrane

A biological membrane or biomembrane is an enclosing or separating amphipathic layer that acts as a barrier within or around a cell . It is, almost invariably, a lipid bilayer, composed of a double layer of lipid-class molecules, specifically phospholipids and cholesterol, with occasional integral membrane protein intertwined, some o...
. Such a protein may cross the membrane only once or it may weave in and out, crossing several times. TM proteins can be categorized as Type I, which are positioned such that their amino-terminus is outside of the membrane, or Type II, which have their carboxy-terminus outside of the membrane.

Integral monotopic proteins

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 (cyclooxygenase
    Cyclooxygenase

    Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids . Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain; this is the method of action of non-steroidal anti-inflammatory drugs, such as the well-known aspirin and ibuprofen....
    s) ,
  • lanosterol synthase
    Lanosterol synthase

    Lanosterol synthase is an enzyme that converts 2,3-oxidosqualene to a protosterol cation and finally to lanosterol.External links...
     and squalene-hopene cyclase ,
  • microsomal prostaglandin E synthase
    Prostaglandin E synthase

    Prostaglandin E synthase is an enzyme involved in eicosanoid and glutathione metabolism, a member of MAPEG family. It generates prostaglandin E from prostaglandin H2....
     ,
  • carnitine O-palmitoyltransferase
    Carnitine O-palmitoyltransferase

    Carnitine O-palmitoyltransferase is a mitochondrial transferase enzyme involved in the metabolism of palmitoylcarnitine into palmitoyl-CoA....
     2 .


There are also structures of integral monotopic domains of transmembrane proteins:
  • monoamine oxidase
    Monoamine oxidase

    Monoamine oxidases are enzymes that catalysis the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body....
    s A and B ,
  • fatty acid amide hydrolase ,
  • mammalian cytochrome P450 oxidase
    Cytochrome P450 oxidase

    Cytochrome P450 is a very large and diverse superfamily of hemoproteins found in all domains of life. Cytochromes P450 use a plethora of both exogenous and endogenous compounds as substrates in enzymatic reactions....
    s ,
  • corticosteroid 11-beta-dehydrogenases .
Such domains require detergents for extraction or crystallization, even after removal of their transmembrane helices. Therefore, they are often classified as integral monotopic proteins

Function

IMPs include transporters, channels
Ion channel

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cell s by allowing the flow of ions down their electrochemical gradient....
, receptors
Receptor (biochemistry)

In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach....
, enzymes, structural membrane-anchoring domains, proteins involved in accumulation and transduction
Transduction (biophysics)

In biophysics, transduction is the conveyance of energy from one electron to another , at the same time that the class of energy changes.Photonic energy, the kinetic energy of a photon, may follow the following paths:...
 of energy, and proteins responsible for cell adhesion
Cell adhesion

Cellular adhesion is the binding of a cell to another cell or to a surface or extracellular matrix. Cellular adhesion is regulated by specific cell adhesion molecules that interact with other molecules....
. Classification of transporters can be found in .

Examples

Examples of integral membrane proteins:
  • Integrin
    Integrin

    Integrins are cell surface receptors that interact with the extracellular matrix and mediate various cell signaling. They define cellular shape, mobility, and regulate the cell cycle....
  • Cadherin
    Cadherin

    Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together....
  • Insulin receptor
    Insulin receptor

    In molecular biology, the insulin receptor is a transmembrane receptor receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors....
  • NCAM
  • Selectin
    Selectin

    Selectins are a family of cell adhesion molecules . All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus and calcium-dependent binding....
  • Some types of cell adhesion
    Cell adhesion

    Cellular adhesion is the binding of a cell to another cell or to a surface or extracellular matrix. Cellular adhesion is regulated by specific cell adhesion molecules that interact with other molecules....
     proteins
  • Some types of receptor proteins
    Transmembrane receptor

    Transmembrane receptors are integral membrane proteins, which reside and operate typically within a cell's plasma membrane, but also in the biological membrane of some subcellular compartments and organelles....
  • Glycophorin
    Glycophorin

    A Glycophorin is a sialoglycoprotein of the membrane of a red blood cell. It is a membrane-spanning protein and carries sugar molecules.A major example is Glycophorin C....
  • Rhodopsin
    Rhodopsin

    Rhodopsin, also known as visual purple, is a pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light....
  • Band 3
    Band 3

    Anion Exchanger 1 or Band 3 is a phylogenetically preserved transport protein responsible for mediating the electroneutral exchange of chloride for bicarbonate across a plasma membrane....
  • CD36
    CD36

    CD36 is an integral membrane protein found on the surface of many cell types in vertebrate animals and is also known as FAT, SCARB3, GP88, glycoprotein IV and glycoprotein IIIb ....


See also

  • Membrane protein
    Membrane protein

    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....
    s
  • Transmembrane protein
    Transmembrane protein

    A transmembrane protein is a protein that spans the entire biological membrane. Transmembrane proteins aggregate and precipitate in water. They require detergents or nonpolar solvents for extraction, although some of them can be also extracted using denaturing agents....
    s
  • Peripheral membrane protein
    Peripheral membrane protein

    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....
    s


External links

  • Database of 3D structures of integral membrane proteins and hydrophobic peptides with emphasis on crystallization conditions
  • from Stephen White laboratory
  • Calculated spatial positions of transmembrane, integral monotopic, and peripheral proteins in membranes