APOBEC: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
consistent citation formatting
I expanded on the existing information in the introduction.
Line 35: Line 35:
'''APOBEC''' ("apolipoprotein B mRNA editing enzyme, catalytic polypeptide") is a family of evolutionarily conserved [[cytidine deaminase]]s.
'''APOBEC''' ("apolipoprotein B mRNA editing enzyme, catalytic polypeptide") is a family of evolutionarily conserved [[cytidine deaminase]]s.


A mechanism of generating protein diversity is [[messenger RNA|mRNA]] editing. Members of this family are [[RNA editing#C-U editing|C-to-U editing]] enzymes. The [[N-terminus|N-terminal]] domain of APOBEC like proteins is the catalytic domain, while the [[C-terminus|C-terminal]] domain is a pseudocatalytic domain. More specifically, the catalytic domain is a zinc dependent cytidine deaminase domain and is essential for cytidine deamination. RNA editing by APOBEC-1 requires homodimerisation and this complex interacts with RNA binding proteins to form the [[editosome]].<ref name="pmid12683974">{{cite journal | vauthors = Wedekind JE, Dance GS, Sowden MP, Smith HC | title = Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business | journal = Trends in Genetics | volume = 19 | issue = 4 | pages = 207–216 | date = April 2003 | pmid = 12683974 | doi = 10.1016/S0168-9525(03)00054-4 }}</ref>
A mechanism of generating protein diversity is [[messenger RNA|mRNA]] editing. The APOBEC family of proteins perform mRNA modifications by deaminating cytidine bases to uracil. The [[N-terminus|N-terminal]] domain of APOBEC like proteins is the catalytic domain, while the [[C-terminus|C-terminal]] domain is a pseudocatalytic domain. More specifically, the catalytic domain is a zinc dependent cytidine deaminase domain and is essential for cytidine deamination. The positively charged zinc ion in the catalytic domain attracts to the partial-negative charge of RNA.


In the case of APOBEC-1, the mRNA transcript of intestinal apolipoprotein B is truncated. RNA editing by APOBEC-1 requires homodimerization and this complex interacts with RNA binding proteins to form the [[editosome]].<ref name="pmid12683974">{{cite journal | vauthors = Wedekind JE, Dance GS, Sowden MP, Smith HC | title = Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business | journal = Trends in Genetics | volume = 19 | issue = 4 | pages = 207–216 | date = April 2003 | pmid = 12683974 | doi = 10.1016/S0168-9525(03)00054-4 }}</ref> The resulting structure interacts with the codon CAA and deaminates it into UAA, producing a stop codon. For other APOBEC proteins such as in the site-specific deamination of a CGA to a UGA stop codon in neurofibromatosis type 1, the resulting proteins are predicted to be truncated as well.<ref>{{Cite journal |last=Blanc |first=Valerie |last2=Davidson |first2=Nicholas O. |date=2003-01 |title=C-to-U RNA Editing: Mechanisms Leading to Genetic Diversity |url=https://doi.org/10.1074/jbc.R200024200 |journal=Journal of Biological Chemistry |volume=278 |issue=3 |pages=1395–1398 |doi=10.1074/jbc.r200024200 |issn=0021-9258}}</ref>
⚫
In humans/mammals they help protect from viral infections.<ref name=APOBEC3-2016/><ref name="pmid34353635">{{cite journal | vauthors = Cervantes-Gracia K, Gramalla-Schmitz A, Weischedel J, Chahwan R | title = APOBECs orchestrate genomic and epigenomic editing across health and disease | journal = Trends in Genetics | volume = 37 | issue = 11 | pages = 1028–1043 | date = November 2021 | pmid = 34353635 | doi = 10.1016/j.tig.2021.07.003 | s2cid = 236934922 | doi-access = free }}</ref> These enzymes, when misregulated, are a major source of mutation in numerous cancer types.<ref name=APOBEC3-2016>{{cite web |url=http://www.genengnews.com/gen-news-highlights/unexpected-dna-binding-mechanism-suggests-ways-to-block-enzyme-activity-in-cancer/81253584 |title=''Unexpected DNA-Binding Mechanism Suggests Ways to Block Enzyme Activity in Cancer'' |date=Dec 2016 |quote=Based on ("Structural Basis for Targeted DNA Cytosine Deamination and Mutagenesis by APOBEC3A and APOBEC3B") online in Nature Structural and Molecular Biology. }}</ref><ref name="pmid34353635"/><ref>{{cite journal | vauthors = Butler K, Banday AR | title = APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential | journal = Journal of Hematology & Oncology | volume = 16 | issue = 1 | pages = 31 | date = March 2023 | pmid = 36978147 | pmc = 10044795 | doi = 10.1186/s13045-023-01425-5 | doi-access = free }}</ref>

C-to-U modifications do not always result in the truncation of proteins. For example, in humans/mammals they help protect from viral infections.<ref name="APOBEC3-2016" /><ref name="pmid34353635">{{cite journal | vauthors = Cervantes-Gracia K, Gramalla-Schmitz A, Weischedel J, Chahwan R | title = APOBECs orchestrate genomic and epigenomic editing across health and disease | journal = Trends in Genetics | volume = 37 | issue = 11 | pages = 1028–1043 | date = November 2021 | pmid = 34353635 | doi = 10.1016/j.tig.2021.07.003 | s2cid = 236934922 | doi-access = free }}</ref> APOBEC family proteins are widely expressed in cells of the human innate immune system.<ref>{{Cite journal |last=Koito |first=Atsushi |last2=Ikeda |first2=Terumasa |date=2013 |title=Intrinsic immunity against retrotransposons by APOBEC cytidine deaminases |url=https://www.frontiersin.org/articles/10.3389/fmicb.2013.00028 |journal=Frontiers in Microbiology |volume=4 |doi=10.3389/fmicb.2013.00028 |issn=1664-302X |pmc=PMC3576619 |pmid=23431045}}</ref>

⚫
These enzymes, when misregulated, are a major source of mutation in numerous cancer types.<ref name="APOBEC3-2016">{{cite web |url=http://www.genengnews.com/gen-news-highlights/unexpected-dna-binding-mechanism-suggests-ways-to-block-enzyme-activity-in-cancer/81253584 |title=''Unexpected DNA-Binding Mechanism Suggests Ways to Block Enzyme Activity in Cancer'' |date=Dec 2016 |quote=Based on ("Structural Basis for Targeted DNA Cytosine Deamination and Mutagenesis by APOBEC3A and APOBEC3B") online in Nature Structural and Molecular Biology. }}</ref><ref name="pmid34353635" /><ref>{{cite journal | vauthors = Butler K, Banday AR | title = APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential | journal = Journal of Hematology & Oncology | volume = 16 | issue = 1 | pages = 31 | date = March 2023 | pmid = 36978147 | pmc = 10044795 | doi = 10.1186/s13045-023-01425-5 | doi-access = free }}</ref> When the expression of APOBEC family proteins is triggered, accidental mutations in somatic cells can lead to the development of oncogenes, cells which have the potential to develop into a tumor. APOBEC proteins are further expressed in attempt to regulate tumor formation. This makes APOBEC proteins a helpful marker for diagnosing malignant tumors.<ref>{{Citation |last=Okazaki |first=Il‐mi |title=Role of AID in Tumorigenesis |date=2007-01-01 |url=https://www.sciencedirect.com/science/article/pii/S0065277606940085 |work=Advances in Immunology |volume=94 |pages=245–273 |access-date=2023-11-28 |series=AID for Immunoglobulin Diversity |publisher=Academic Press |doi=10.1016/s0065-2776(06)94008-5 |last2=Kotani |first2=Ai |last3=Honjo |first3=Tasuku}}</ref>


A 2013 review discussed the structural and biophysical aspects of APOBEC3 family enzymes.<ref>{{cite journal | vauthors = Vasudevan AA, Smits SH, Höppner A, Häussinger D, Koenig BW, Münk C | title = Structural features of antiviral DNA cytidine deaminases | journal = Biological Chemistry | volume = 394 | issue = 11 | pages = 1357–1370 | date = November 2013 | pmid = 23787464 | doi = 10.1515/hsz-2013-0165 | s2cid = 4151961 | url = http://juser.fz-juelich.de/record/139785/files/FZJ-2013-05757.pdf }}</ref> Many of the APOBEC protein features are described in the widely studied [[APOBEC3G]]'s page.{{tone inline|date=June 2022}}
A 2013 review discussed the structural and biophysical aspects of APOBEC3 family enzymes.<ref>{{cite journal | vauthors = Vasudevan AA, Smits SH, Höppner A, Häussinger D, Koenig BW, Münk C | title = Structural features of antiviral DNA cytidine deaminases | journal = Biological Chemistry | volume = 394 | issue = 11 | pages = 1357–1370 | date = November 2013 | pmid = 23787464 | doi = 10.1515/hsz-2013-0165 | s2cid = 4151961 | url = http://juser.fz-juelich.de/record/139785/files/FZJ-2013-05757.pdf }}</ref> Many of the APOBEC protein features are described in the widely studied [[APOBEC3G]]'s page.{{tone inline|date=June 2022}}

Revision as of 17:35, 28 November 2023

Example of a member of the APOBEC family, APOBEC-2. A cytidine deaminase from Homo sapiens.[1]
APOBEC-like N-terminal domain
Identifiers
SymbolAPOBEC_N
PfamPF08210
InterProIPR013158
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
APOBEC-like C-terminal domain
Identifiers
SymbolAPOBEC_C
PfamPF05240
InterProIPR007904
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

APOBEC ("apolipoprotein B mRNA editing enzyme, catalytic polypeptide") is a family of evolutionarily conserved cytidine deaminases.

A mechanism of generating protein diversity is mRNA editing. The APOBEC family of proteins perform mRNA modifications by deaminating cytidine bases to uracil. The N-terminal domain of APOBEC like proteins is the catalytic domain, while the C-terminal domain is a pseudocatalytic domain. More specifically, the catalytic domain is a zinc dependent cytidine deaminase domain and is essential for cytidine deamination. The positively charged zinc ion in the catalytic domain attracts to the partial-negative charge of RNA.

In the case of APOBEC-1, the mRNA transcript of intestinal apolipoprotein B is truncated. RNA editing by APOBEC-1 requires homodimerization and this complex interacts with RNA binding proteins to form the editosome.[2] The resulting structure interacts with the codon CAA and deaminates it into UAA, producing a stop codon. For other APOBEC proteins such as in the site-specific deamination of a CGA to a UGA stop codon in neurofibromatosis type 1, the resulting proteins are predicted to be truncated as well.[3]

C-to-U modifications do not always result in the truncation of proteins. For example, in humans/mammals they help protect from viral infections.[4][5] APOBEC family proteins are widely expressed in cells of the human innate immune system.[6]

These enzymes, when misregulated, are a major source of mutation in numerous cancer types.[4][5][7] When the expression of APOBEC family proteins is triggered, accidental mutations in somatic cells can lead to the development of oncogenes, cells which have the potential to develop into a tumor. APOBEC proteins are further expressed in attempt to regulate tumor formation. This makes APOBEC proteins a helpful marker for diagnosing malignant tumors.[8]

A 2013 review discussed the structural and biophysical aspects of APOBEC3 family enzymes.[9] Many of the APOBEC protein features are described in the widely studied APOBEC3G's page.[tone]

Family members

Human genes encoding members of the APOBEC protein family include:

References

  1. ^ PDB: 2NYT​; Prochnow C, Bransteitter R, Klein MG, Goodman MF, Chen XS (January 2007). "The APOBEC-2 crystal structure and functional implications for the deaminase AID". Nature. 445 (7126): 447–451. Bibcode:2007Natur.445..447P. doi:10.1038/nature05492. PMID 17187054. S2CID 4394772.; rendered using PyMOL.
  2. ^ Wedekind JE, Dance GS, Sowden MP, Smith HC (April 2003). "Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business". Trends in Genetics. 19 (4): 207–216. doi:10.1016/S0168-9525(03)00054-4. PMID 12683974.
  3. ^ Blanc, Valerie; Davidson, Nicholas O. (2003-01). "C-to-U RNA Editing: Mechanisms Leading to Genetic Diversity". Journal of Biological Chemistry. 278 (3): 1395–1398. doi:10.1074/jbc.r200024200. ISSN 0021-9258. {{cite journal}}: Check date values in: |date= (help)CS1 maint: unflagged free DOI (link)
  4. ^ a b "Unexpected DNA-Binding Mechanism Suggests Ways to Block Enzyme Activity in Cancer". Dec 2016. Based on ("Structural Basis for Targeted DNA Cytosine Deamination and Mutagenesis by APOBEC3A and APOBEC3B") online in Nature Structural and Molecular Biology.
  5. ^ a b Cervantes-Gracia K, Gramalla-Schmitz A, Weischedel J, Chahwan R (November 2021). "APOBECs orchestrate genomic and epigenomic editing across health and disease". Trends in Genetics. 37 (11): 1028–1043. doi:10.1016/j.tig.2021.07.003. PMID 34353635. S2CID 236934922.
  6. ^ Koito, Atsushi; Ikeda, Terumasa (2013). "Intrinsic immunity against retrotransposons by APOBEC cytidine deaminases". Frontiers in Microbiology. 4. doi:10.3389/fmicb.2013.00028. ISSN 1664-302X. PMC 3576619. PMID 23431045.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  7. ^ Butler K, Banday AR (March 2023). "APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential". Journal of Hematology & Oncology. 16 (1): 31. doi:10.1186/s13045-023-01425-5. PMC 10044795. PMID 36978147.
  8. ^ Okazaki, Il‐mi; Kotani, Ai; Honjo, Tasuku (2007-01-01), "Role of AID in Tumorigenesis", Advances in Immunology, AID for Immunoglobulin Diversity, vol. 94, Academic Press, pp. 245–273, doi:10.1016/s0065-2776(06)94008-5, retrieved 2023-11-28
  9. ^ Vasudevan AA, Smits SH, Höppner A, Häussinger D, Koenig BW, Münk C (November 2013). "Structural features of antiviral DNA cytidine deaminases" (PDF). Biological Chemistry. 394 (11): 1357–1370. doi:10.1515/hsz-2013-0165. PMID 23787464. S2CID 4151961.
This article incorporates text from the public domain Pfam and InterPro: IPR013158
Stub icon

This protein-related article is a stub. You can help Wikipedia by expanding it.

Retrieved from "https://en.wikipedia.org/w/index.php?title=APOBEC&oldid=1187343822"