
A single-pass membrane protein also known as single-spanning protein or bitopic protein is a
transmembrane protein that spans the
lipid bilayer only once.
These proteins may constitute up to 50% of all
transmembrane proteins, depending on the organism, and contribute significantly to
the network of interactions between different proteins in cells, including interactions via transmembrane
alpha helices.
They usually include one or several water-soluble
domains situated at the different sides of
biological membrane
A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates the interior of a cell from the external environment or creates intracellular compartments by serving as a boundary between one part of the ce ...
s, for example in single-pass
transmembrane receptors. Some of them are small and serve as regulatory or structure-stabilizing subunits in large multi-protein transmembrane complexes, such as
photosystems or the
respiratory chain. A 2013 estimate identified about 1300 single-pass membrane proteins in the
human genome.
Topology-based classification
Bitopic proteins are classified into 4 types, depending on their
transmembrane topology and location of the transmembrane helix in the amino acid sequence of the protein. According to
Uniprot:
* ''Type I:''
N-terminus
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 ami ...
on the extracellular side of the membrane; removed
signal peptide
A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-ter ...
* ''Type II:'' N-terminus on the cytoplasmic side of the membrane; transmembrane helix located close to the N-terminus, where it works as an anchor
* ''Type III:'' N-terminus on the extracellular side of the membrane; no
signal peptide
A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-ter ...
* ''Type IV:'' N-terminus on the cytoplasmic side of the membrane; transmembrane helix located close to the C-terminus, where it works as an anchor
Hence type I proteins are anchored to the lipid membrane with a stop-transfer anchor sequence and have their N-terminal domains
targeted to the ER lumen during synthesis. Type II and III are anchored with a signal-anchor sequence, with type II being targeted to the ER lumen with its C-terminal domain, while type III have their N-terminal domains targeted to the ER lumen.
Structure
A single-pass transmembrane protein typically consists of three domains, the
extracellular domain, the
transmembrane domain, and the
intracellular domain. The transmembrane domain is the smallest at around 25
amino acid residue
Protein structure is the molecular geometry, three-dimensional arrangement of atoms in an amino acid-chain molecule. Proteins are polymers specifically polypeptides formed from sequences of amino acids, the monomers of the polymer. A single ami ...
s and forms an
alpha helix
The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...
inserted into the membrane bilayer. The ECD is typically much larger than the ICD and is often
globular, whereas many ICDs have relatively high
disorder.
Some proteins in this class function as monomers, but dimerization or higher-order oligomerization is common.
Evolution
The number of single-pass transmembrane proteins in an organism's
genome varies significantly. It is higher in
eukaryote
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
s than
prokaryotes
A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
and in
multicellular than
unicellular organisms.
The fraction of proteins in this class is larger in humans than in the
model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
s ''
Danio rerio'' (zebrafish) and ''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...
'' (nematode worms), suggesting that genes encoding these proteins have undergone expansion in the
vertebrate and
mammalian lineages.
Databases
*
Membranome database
Membranome database provides structural and functional information about more than 6000 single-pass (bitopic) transmembrane proteins from ''Homo sapiens'', ''Arabidopsis thaliana'', ''Dictyostelium discoideum'', ''Saccharomyces cerevisiae'', '' ...
is a database of bitopic proteins from several model organisms.
Bitopic proteinsin
OPM database
References
Single-pass transmembrane proteins
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