Transmembrane domain usually denotes a single transmembrane alpha helix of a transmembrane protein. It is called a "domain" because an alpha-helix in a membrane can be folded independently from the rest of the protein, similar to domains of water-soluble proteins. More broadly, a transmembrane domain is any three-dimensional protein structure which is thermodynamically stable in a membrane. This may be a single alpha helix, a stable complex of several transmembrane alpha helices, a transmembrane beta barrel, a beta-helix of gramicidin A, or any other structure.
Transmembrane helices are usually about 20 amino acids in length, although they may be much longer or shorter.
Identification of transmembrane helices
Transmembrane helices are visible in structures of membrane proteins determined by X-ray diffraction. They may also be predicted on the basis of hydrophobicity. Because the interior of the bilayer and the interiors of most proteins of known structure are hydrophobic, it is presumed to be a requirement of the amino acids that span a membrane that they be hydrophobic as well. However, membrane pumps and ion channels also contain numerous charged and polar residues within the generally non-polar transmembrane segments.
Using hydrophobicity analysis to predict transmembrane helices enables a prediction in turn of the "transmembrane topology" of a protein; i.e. prediction of what parts of it protrude into the cell, what parts protrude out, and how many times the protein chain crosses the membrane. Such prediction methods are commonly applied with a limited success.
The Bioinformatics package STRAP provides access to 15 different TM-helix prediction algorithms.