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

* ''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 proteins
in OPM database

References

Single-pass transmembrane proteins {{biology-stub