L27 Domain
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The L27 domain is a
protein domain In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, thre ...
that is found in receptor targeting proteins Lin-2 and Lin-7 (
LIN7A Lin-7 homolog A is a protein that in humans is encoded by the ''LIN7A'' gene. Interactions LIN7A has been shown to interact with: * CASK, * DLG1 Discs large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a scaffo ...
,
LIN7B Lin-7 homolog B is a protein that in humans is encoded by the ''LIN7B'' gene. Interactions LIN7B has been shown to interact with: * ACCN3, * GRIN2B Glutamate MDAreceptor subunit epsilon-2, also known as ''N''-methyl D-aspartate receptor su ...
, LIN7C), as well as some
protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them ( phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a f ...
s and human
MPP2 MAGUK p55 subfamily member 2 is a protein that in humans is encoded by the ''MPP2'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that ...
protein. The L27 domain is a
protein interaction Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
module that exists in a large family of scaffold proteins, functioning as an organisation centre of large protein assemblies required for the establishment and maintenance of
cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...
polarity. L27 domains form specific heterotetrameric complexes, in which each domain contains three
alpha-helices An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...
. The L27_2 domain is a protein-protein interaction domain capable of organising
scaffold protein In biology, scaffold proteins are crucial regulators of many key signalling pathways. Although scaffolds are not strictly defined in function, they are known to interact and/or bind with multiple members of a signalling pathway, tethering them in ...
s into supramolecular assemblies by formation of
heteromeric A heteromer is something that consists of different parts; the antonym of homomeric. Examples are: Biology * Spinal neurons that pass over to the opposite side of the spinal cord. * A protein complex that contains two or more different polypeptid ...
L27_2 domain complexes. L27_2 domain-mediated
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
assemblies have been shown to play essential roles in cellular processes including asymmetric
cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
, establishment and maintenance of
cell polarity Cell polarity refers to spatial differences in shape, structure, and function within a cell. Almost all cell types exhibit some form of polarity, which enables them to carry out specialized functions. Classical examples of polarized cells are de ...
, and clustering of
receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
s and
ion channels Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ...
. Members of this family form specific heterotetrameric complexes, in which each domain contains three
alpha-helices An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...
. The two
N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
helices A helix (; ) is a shape like a cylindrical coil spring or the thread of a machine screw. It is a type of smoothness (mathematics), smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as ...
of each L27_2 domain pack together to form a tight, four-helix bundle in the
heterodimer In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...
, whilst the third
helix A helix (; ) is a shape like a cylindrical coil spring or the thread of a machine screw. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is for ...
of each L27_2 domain forms another four-helix bundle that assembles the two units of the
heterodimer In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...
into a
tetramer A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula ...
. The L27_N domain is often found at the N-terminus of the L27 domain. It plays a role in the
biogenesis Spontaneous generation is a Superseded scientific theories, superseded scientific theory that held that living creatures could arise from abiotic component, non-living matter and that such processes were commonplace and regular. It was Hypoth ...
of
tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein Cell junction, junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. Th ...
s and in the establishment of cell polarity in
epithelial cell Epithelium or epithelial tissue is a thin, continuous, protective layer of Cell (biology), cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial (Mesothelium, mesothelial) tissues line ...
s. Each L27_N domain consists of three alpha-helices, the first two of which form an antiparallel
coiled-coil A coiled coil is a structural motif in proteins in which two to seven alpha-helices are coiled together like the strands of a rope. ( Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a v ...
. Two L27 domains come together to form a four-helical bundle with the antiparallel coiled-coils formed by the first two
helices A helix (; ) is a shape like a cylindrical coil spring or the thread of a machine screw. It is a type of smoothness (mathematics), smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as ...
. The third
helix A helix (; ) is a shape like a cylindrical coil spring or the thread of a machine screw. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is for ...
of each domain forms another coiled-coil packing at one end of the four-helix bundle, creating a large
hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...
interface: the
hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...
interactions are the major force that drives
heterodimer In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...
formation.


References


Further reading

* Protein domains Protein structure {{protein-stub