Biomedical Engineering Reference
In-Depth Information
On the functional point of view, membrane proteins perform a variety of
functions, including the transport of ions and molecules across the membrane,
bind to small molecules at the extracellular space, recognize the immune system,
cell-cell signaling and energy transducers. Transporters are one of the major classes
of membrane proteins that span the cell membrane and form an intricate system of
pumps and channels through which they deliver essential nutrients, eject waste
products, and assist the cell to sense environmental conditions. Transporters repre-
sent a diverse group of proteins that differ in membrane topology, energy coupling
mechanism, and substrate specificities [
3
,
4
]. Transporters are generally classified
into channels/pores, electrochemical and active transporters along with other minor
classes, group translocators, transport electron carriers, accessory factors involved
in transport and incompletely characterized transport systems [
5
].
The classifications of membrane proteins based on their structure and function
are important problems toward the advancement of structural and functional geno-
mics. In this review, we focus on various discrimination algorithms developed for
the classification of membrane proteins based on their structures, TMH and TMS
proteins as well as their functions, especially different classes and families of
transporters. In the first part, we discuss the features of transmembrane proteins,
algorithms for discriminating TMH proteins and predicting their membrane span-
ning regions. Further, we mention the principles of
-barrel membrane proteins
along with discrimination/prediction methods. In the second part, the characteristic
features of amino acid residues in different classes and families of membrane
transporters will be outlined and the discrimination methods for classifying
channels, pores, electrochemical and active transporters will be presented. Further,
the subclassification of ion channels and drug-target interactions will be discussed.
b
2 Databases for Membrane Proteins Based
on Their Structures
The three-dimensional structures of proteins and their complexes are complied in
Protein Data Bank (PDB) [
6
]. Based on the PDB, several other databases have been
developed for different sets of proteins, and specifically for membrane proteins.
Tusnady et al. [
7
] developed a database of transmembrane proteins, PDBTM, which
includes the sequences and structures of redundant and nonredundant
a
-helical and
b
-barrel membrane proteins along with their membrane spanning segments.
Jeyasinghe et al. [
8
] compiled the structures of known membrane proteins, MPtopo
and classified them into several groups, such as monotopic, GPCRs, rhodopsins,
and
-barrel membrane proteins. They have included the PDB codes, structures,
and their respective references. Ikeda et al. [
9
] developed a database of transmem-
brane protein topologies, TMPDB, which is based on the experimental evidences
from X-ray crystallography, NMR spectroscopy, etc. These databases provide
additional information on nonredundant structures, options to search the database
b
