Dispanin

In molecular biology, the protein family Dispanin is another name for Interferon-induced transmembrane protein (IFITM). This refers to a family of protein domains which have a specific formation, or in other words, topology containing two alpha helices in within the cell membrane which are called two transmembrane proteins. This includes proteins such as CD225 (Cluster of Differentiation 225).[1] The function of this protein family is to inhibit cell invasion of many harmful, pathogenic viruses, such as HIV. Henceforth, they are being intensively studied in the hope of drug discovery. They mediate the immune response by interferons.

CD225
Identifiers
SymbolCD225
PfamPF04505
InterProIPR007593

Function

Dispanins have a wide range of functions within the organism. It has a role to play in oncogenesis and germ cell development ([1] as well as cell adhesion and cell signalling.[2]

In particular, IFITMs prevent HIV infection by preventing the virus from entering the host cell.[2] It does this by S-palmitoylation, a process where fatty acids are added to an amino acid named cysteine.[3] The process is crucial to the protein's antiviral properties and is of huge interest in research. Through studying Dispanin, it is hoped that its antiviral properties can be exploited, and then distributed in the form of medicines and vaccines.

Additionally, a type of dispanin, IFITM5, is expressed in cells that make bone, named osteoblasts. This is due to the important role dispanins play in strengthening the bone by bone mineralization.[1][2]

Structure

This protein family has two transmembrane helices.[1] The precise crystal structure remains to be elucidated.

Sequence Motifs

The sequences across a vast array of organisms, from bacteria to high level eukaryotes all contain the similar sequence motifs; in particular, double cysteine motif in the first transmembrane helix. This motif has recently been shown to undergo post-translational modification through S-palmitoylation. This is important since it increases hydrophobicity, and increases its anti-viral properties.[1]

Evolutionary history

Dispanins in eukaryotes and bacteria have high sequence similarities and share several conserved sequence motifs indication a common evolutionary ancestor.[1]

Human genes

There are a number of human genes which encode for Dispanin proteins, they are as listed below:[1]

  • IFITM: IFITM1, IFITM2, IFITM3, IFITM4
  • PRRT2
  • AC023157
  • AL160276
  • AC068580
  • DSPC2
  • TMEM233
  • TMEM90A
  • TMEM90B
  • TMEM91
  • TUSC5

References
  1. Sällman Almén M, Bringeland N, Fredriksson R, Schiöth HB (2012). "The dispanins: a novel gene family of ancient origin that contains 14 human members". PLOS ONE. 7 (2): e31961. Bibcode:2012PLoSO...731961S. doi:10.1371/journal.pone.0031961. PMC 3282796. PMID 22363774.
  2. Lu J, Pan Q, Rong L, He W, Liu SL, Liang C (2011). "The IFITM proteins inhibit HIV-1 infection". J Virol. 85 (5): 2126–37. doi:10.1128/JVI.01531-10. PMC 3067758. PMID 21177806.
  3. Yount JS, Moltedo B, Yang YY, Charron G, Moran TM, López CB, et al. (2010). "Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3". Nat Chem Biol. 6 (8): 610–4. doi:10.1038/nchembio.405. PMC 2928251. PMID 20601941.
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