The major intrinsic protein (MIP) family is large and diverse, possessing over 100 members that form transmembrane channels. These channel proteins function in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2 and possibly ion transport, by an energy independent mechanism. They are found ubiquitously in bacteria, archaea and eukaryotes.The MIP family contains two major groups of channels: aquaporins and glycerol facilitators. The known aquaporins cluster loosely together as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport water (but not glycerol) while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast FPS protein and tobacco NtTIPA may transport both water and small solutes. The structures of various members of the MIP family have been determined by means of X-ray diffraction [, , ], revealing the fold to comprise a right-handed bundle of 6 transmembrane (TM) α-helices [, , ]. Similarities in the N-and C-terminal halves of the molecule suggest that the proteins may have arisen through tandem, intragenic duplication of an ancestral protein that contained 3 TM domains [].
Mirror-image polydactyly of hands and feet (MIP) is a very rare congenital anomaly characterised by mirror-image duplication of digits. A chromosomal aberration involving mirror-image polydactyly gene 1 (MIPOL1) suggests this to be a good candidate gene for the MIP type of anomaly []. This entry represents the MIPOL1 protein.
The major intrinsic protein (MIP) family is large and diverse, possessing over 100 members that form transmembrane channels. These channel proteins function in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2 and possibly ion transport, by an energy independent mechanism. They are found ubiquitously in bacteria, archaea and eukaryotes.The MIP family contains two major groups of channels: aquaporins and glycerol facilitators. The known aquaporins cluster loosely together as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport water (but not glycerol) while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast FPS protein and tobacco NtTIPA may transport both water and small solutes. The structures of various members of the MIP family have been determined by means of X-ray diffraction [, , ], revealing the fold to comprise a right-handed bundle of 6 transmembrane (TM) α-helices [, , ]. Similarities in the N-and C-terminal halves of the molecule suggest that the proteins may have arisen through tandem, intragenic duplication of an ancestral protein that contained 3 TM domains []. This entry represents a conserved region which is located in the cytoplasmic loop between the second and third transmembrane regions of MIP family members.
The major intrinsic protein (MIP) family is large and diverse, possessing over 100 members that form transmembrane channels. These channel proteins function in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2 and possibly ion transport, by an energy independent mechanism. They are found ubiquitously in bacteria, archaea and eukaryotes.The MIP family contains two major groups of channels: aquaporins and glycerol facilitators. The known aquaporins cluster loosely together as do the known glycerol facilitators. MIP family proteins are believed to form aqueous pores that selectively allow passive transport of their solute(s) across the membrane with minimal apparent recognition. Aquaporins selectively transport water (but not glycerol) while glycerol facilitators selectively transport glycerol but not water. Some aquaporins can transport NH3 and CO2. Glycerol facilitators function as solute nonspecific channels, and may transport glycerol, dihydroxyacetone, propanediol, urea and other small neutral molecules in physiologically important processes. Some members of the family, including the yeast FPS protein and tobacco NtTIPA may transport both water and small solutes. The structures of various members of the MIP family have been determined by means of X-ray diffraction [, , ], revealing the fold to comprise a right-handed bundle of 6 transmembrane (TM) α-helices [, , ]. Similarities in the N-and C-terminal halves of the molecule suggest that the proteins may have arisen through tandem, intragenic duplication of an ancestral protein that contained 3 TM domains []. This superfamily represents the aquaporin-like structural domain.
Legionella pneumophila, the causative agent of Legionnaire's disease, is a facultative intracellular microbe that commonly infects human lung monocytes and macrophages and causes pneumonia []. It is water-borne and highly virulent, relying on several specific pathogenic factors to invade and infect the alveolar tissue. However, once grown to stationary phase in culture, the pathogen spontaneously converts to an avirulent state []. The major virulence factor expressed by Legionella pneumophila is the macrophage infectivity potentiator (Mip) []. Site-directed mutagenesis studies of this protein in vitro severely impaired the intracellular infection of human macrophages by L. pneumophila, causing it to lose its potent antigenic activity []. Further studies into the enzymatic activity of Mip have revealed that it plays a similar role to eukaryotic FK506-binding proteins. In vivo, it acts as a peptidyl-prolyl-cis/trans- isomerase (PPIase) on oligopeptides [], although it is unclear whether this forms part of the virulence process. Substitution of Asp142 of the mature protein by Leu severely reduces the PPIase activity of Mip []. The structure of Mip has been resolved to 2.41A by X-ray crystallography [], revealing the virulence factor to exist as a homodimer. Each monomer consists of an N-terminal dimerisation module, a long central connecting α-helix and a conserved PPIase domain at the C terminus.
