iPedia Free Information Center

Information about Transmembrane

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 (beta-barrels) can be also extracted using denaturing agents.

Enlarge picture
Schematic representation of transmembrane proteins: 1. a single transmembrane α-helix (bitopic membrane protein) 2. a polytopic α-helical protein 3. a transmembrane β barrel
The membrane is represented in light brown.

Types

There are two basic types of transmembrane proteins:
  1. Alpha-helical. These proteins are present in all types of biological membranes including outer membranes. This is the major category of transmembrane proteins.
  2. Beta-barrels. These proteins are found only in outer membranes of Gram-negative bacteria, cell wall of Gram-positive bacteria, and outer membranes of mitochondria and chloroplasts. All beta-barrel transmembrane proteins have simplest up-and-down topology, which may reflect their common evolutionary origin and similar folding mechanism.

Thermodynamic stability and folding

Stability of α-helical transmembrane proteins

Transmembrane α-helical proteins are unusually stable judging from thermal denaturation studies, because they do not unfold completely within the membranes (the complete unfolding would require breaking down too many α-helical H-bonds in the nonpolar media). On the other hand, these proteins easily misfold, due to non-native aggregation in membranes, transition to the molten globule states, formation of non-native disulfide bonds, or unfolding of peripheral regions and nonregular loops that are locally less stable.

It is also important to properly define the unfolded state. The unfolded state of membrane proteins in detergent micelles is different from that in the thermal denaturation experiments. This state represents a combination of folded hydrophobic α-helices and partially unfolded segments covered by the detergent. For example, the "unfolded" bacteriorhodopsin in SDS micelles has four transmembrane α-helices folded, while the rest of the protein is situated at the micelle-water interface and can adopt different types of non-native amphiphilic structures. Free energy differences between such detergent-denatured and native states are similar to stabilities of water-soluble proteins (< 10 kcal/mol).

Folding of α-helical transmembrane proteins

Refolding of α-helical transmembrane proteins in vitro is technically difficult. There are relatively few examples of the successful refolding experiments, as for bacteriorhodopsin. In vivo all such proteins are normally folded co-translationally within the large transmembrane translocon. The translocon channel provides a highly heterogeneous environment for the nascent transmembane α-helices. A relatively polar amphiphilic α-helix can adopt a transmembrane orientation in the translocon (although it would be at the membrane surface or unfolded in vitro), because its polar residues can face the central water-filled channel of the translocon. Such mechanism is necessary for incorporation of polar α-helices into structures of transmembrane proteins. The amphiphilic helices remain attached to the translocon until the protein is completely synthesized and folded. If the protein remains unfolded and attached to the translocon for too long, it is degraded by specific "quality control" cellular systems.

Stability and folding of β-barrel transmembrane proteins

Stability of β-barrel transmembrane proteins is similar to stability of water-soluble proteins, based on chemical denaturation studies. Their folding in vivo is facilitated by water-soluble chaperones, such as protein Skp [1].

3D structures

Light absorption-driven transporters

Oxidoreduction-driven transporters

Electrochemical potential-driven transporters

P-P-bond hydrolysis-driven transporters

Porters (uniporters, symporters, antiporters)

Alpha-helical channels including ion channels

Enzymes

Proteins with alpha-helical transmembrane anchors

β-Barrels from outer membranes of Gram-negative bacteria

Note: n and S are number of beta-strands and "share number" [2] of beta-barrel

Oligomeric β-barrels of Gram-positive bacteria

See also Gramicidin A [3], a peptide that forms a dimeric transmembrane β-helix. It is also secreted by Gram-positive bacteria.

References

  • Booth, P.J., Templer, R.H., Meijberg, W., Allen, S.J., Curran, A.R., and Lorch, M. 2001. In vitro studies of membrane protein folding. Crit. Rev. Biochem. Mol. Biol. 36: 501-603.
  • Bowie J.U. 2001. Stabilizing membrane proteins. Curr. Op. Struct. Biol. 11: 397-402.
  • Bowie J.U. 2005. Solving the membrane protein folding problem. Nature 438: 581-589.
  • DeGrado W.F., Gratkowski H. and Lear J.D. 2003. How do helix-helix interactions help determine the folds of membrane proteins? Perspectives from the study of homo-oligomeric helical bundles. Protein Sci. 12: 647-665.
  • Lee, A.G. 2003 Lipid-protein interactions in biological membranes: a structural perspective. Biochim. Biophys. Acta 1612: 1-40.
  • Lee, A.G. 2004. How lipids affect the activities of integral membrane proteins. Biochim. Biophys. Acta 1666: 62-87.
  • le Maire, M., Champeil, P., and Moller, J.V. 2000. Interaction of membrane proteins and lipids with solubilizing detergents. Biochim. Biophys. Acta 1508: 86-111.
  • Popot J-L. and Engelman D.M. 2000. Helical membrane protein folding, stability, and evolution. Annu. Rev. Biochem. 69: 881-922.
  • Protein-lipid interactions (Ed. L.K. Tamm) Wiley, 2005.
  • Tamm, L.K., Hong, H., and Liang, B.Y. 2004. Folding and assembly of beta-barrel membrane proteins. Biochim. Biophys. Acta 1666: 250-263.

Additional examples

External links

See also

See also:
A biological membrane or biomembrane is an enclosing or separating tissue which acts as a barrier within or around a cell.
..... Click the link for more information.
Detergent is a compound, or a mixture of compounds, intended to assist cleaning. The term is often used to differentiate between soap and other chemical surfactants used for cleaning purposes.
..... Click the link for more information.
See also:
A biological membrane or biomembrane is an enclosing or separating tissue which acts as a barrier within or around a cell.
..... Click the link for more information.
The outer membrane refers to the outside membranes of Gram-negative bacteria, the chloroplast, or the mitochondria. It is used to maintain the shape of the organelle contained within its structure, and it acts as a barrier against certain dangers.
..... Click the link for more information.
The outer membrane refers to the outside membranes of Gram-negative bacteria, the chloroplast, or the mitochondria. It is used to maintain the shape of the organelle contained within its structure, and it acts as a barrier against certain dangers.
..... Click the link for more information.
Gram-negative bacteria are those that do not retain crystal violet dye in the Gram staining protocol.[1] Gram-positive bacteria will retain the dark blue dye after an alcohol wash.
..... Click the link for more information.
cell wall is a fairly rigid layer surrounding a cell, located external to the cell membrane, which provides the cell with structural support, protection, and acts as a filtering mechanism. The cell wall also prevents over-expansion when water enters the cell.
..... Click the link for more information.
Gram-positive bacteria are those that retain a crystal violet dye during the Gram stain process.[1] Gram-positive bacteria appear blue or violet under a microscope, while Gram-negative bacteria appear red or pink.
..... Click the link for more information.
The outer membrane refers to the outside membranes of Gram-negative bacteria, the chloroplast, or the mitochondria. It is used to maintain the shape of the organelle contained within its structure, and it acts as a barrier against certain dangers.
..... Click the link for more information.
Editing of this page by unregistered or newly registered users is currently disabled due to vandalism.
If you are prevented from editing this page, and you wish to make a change, please discuss changes on the talk page, request unprotection, log in, or .
..... Click the link for more information.
Chloroplasts are organelles found in plant cells and eukaryotic algae that conduct photosynthesis. Chloroplasts absorb sunlight and use it in conjunction with water and carbon dioxide to produce sugars, the raw material for energy and biomass production in all green plants
..... Click the link for more information.
Transmembrane domain usually denotes a single transmembrane alpha helix of a transmembrane protein. It is called "domain" because an alpha-helix in membrane can be folded independently on the rest of the protein, similar to domains of water-soluble proteins.
..... Click the link for more information.
Denaturation is the alteration of a protein or nucleic acid's shape through some form of external stress (for example, by applying heat, acid or alkali), in such a way that it will no longer be able to carry out its cellular function.
..... Click the link for more information.
hydrogen bond is a special type of dipole-dipole bond that exists between an electronegative atom and a hydrogen atom bonded to another electronegative atom. This type of bond always involves a hydrogen atom, thus the name.
..... Click the link for more information.
A molten globule (MG) is a stable, partially folded protein state found in mildly denaturing conditions such as low pH (generally pH = 2), mild denaturant, or high temperature.
..... Click the link for more information.
In chemistry, a disulfide bond is a single covalent bond derived from the coupling of thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore C-S-S-C.
..... Click the link for more information.
Denaturation is the alteration of a protein or nucleic acid's shape through some form of external stress (for example, by applying heat, acid or alkali), in such a way that it will no longer be able to carry out its cellular function.
..... Click the link for more information.
Detergent is a compound, or a mixture of compounds, intended to assist cleaning. The term is often used to differentiate between soap and other chemical surfactants used for cleaning purposes.
..... Click the link for more information.
Micella redirects here. For the brachiopod genus, see Micella (brachiopod).


A micelle (rarely micella, plural micellae) is an aggregate of surfactant molecules dispersed in a liquid colloid.
..... Click the link for more information.
Denaturation is the alteration of a protein or nucleic acid's shape through some form of external stress (for example, by applying heat, acid or alkali), in such a way that it will no longer be able to carry out its cellular function.
..... Click the link for more information.
Bacteriorhodopsin is a photosynthetic pigment used by archaea, most notably halobacteria. It acts as a proton pump, i.e. it captures light energy and uses it to move protons across the membrane out of the cell.
..... Click the link for more information.
The initialism SDS can abbreviate:
  • Safety Data Sheet
  • Samsung SDS: SI Company of Republic of Korea
  • Satellite Data System
  • Scientific Data Systems, a mainframe computer vendor from the 1960s
  • Secondary database server
  • Service Delivery Systems

..... Click the link for more information.
Amphiphile (from the Greek αμφις, amphis: both and φιλíα, philia: love, friendship) is a term describing a chemical compound possessing both hydrophilic and hydrophobic properties.
..... Click the link for more information.
Bacteriorhodopsin is a photosynthetic pigment used by archaea, most notably halobacteria. It acts as a proton pump, i.e. it captures light energy and uses it to move protons across the membrane out of the cell.
..... Click the link for more information.
The translocon (commonly known as a translocator) is the complex of proteins associated with the translocation of nascent polypeptides into the interior (cisternal or luminal) space of the endoplasmic reticulum (ER) from the cytosol.
..... Click the link for more information.
chaperones are proteins that assist the non-covalent folding/unfolding and the assembly/disassembly of other macromolecular structures, but do not occur in these structures when the latter are performing their normal biological functions.
..... Click the link for more information.
Bacteriorhodopsin is a photosynthetic pigment used by archaea, most notably halobacteria. It acts as a proton pump, i.e. it captures light energy and uses it to move protons across the membrane out of the cell.
..... Click the link for more information.
Rhodopsin, also known as visual purple, is expressed in metazoan photoreceptor cells. It 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.
..... Click the link for more information.
Opsins are a group of light-sensitive 35-55 kDa membrane-bound G protein-coupled receptors of the retinylidene protein family found in photoreceptor cells of the retina. They are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the
..... Click the link for more information.
photosynthetic reaction centre is a protein that is the site of the light reactions of photosynthesis. The reaction centre contains pigments such as chlorophyll and phaeophytin. These absorb light, promoting an electron to a higher energy level within the pigment.
..... Click the link for more information.


This article is copied from an article on Wikipedia.org - the free encyclopedia created and edited by online user community. The text was not checked or edited by anyone on our staff. Although the vast majority of the wikipedia encyclopedia articles provide accurate and timely information please do not assume the accuracy of any particular article. This article is distributed under the terms of GNU Free Documentation License.
Herod_Archelaus


page counter