| A portable hot spot recognition loop transfers sequence preferences from APOBEC family members to activation-induced cytidine deaminase. | |
| | |
MedLine Citation:
|
PMID: 19561087 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Enzymes of the AID/APOBEC family, characterized by the targeted deamination of cytosine to generate uracil within DNA, mediate numerous critical immune responses. One family member, activation-induced cytidine deaminase (AID), selectively introduces uracil into antibody variable and switch regions, promoting antibody diversity through somatic hypermutation or class switching. Other family members, including APOBEC3F and APOBEC3G, play an important role in retroviral defense by acting on viral reverse transcripts. These enzymes are distinguished from one another by targeting cytosine within different DNA sequence contexts; however, the reason for these differences is not known. Here, we report the identification of a recognition loop of 9-11 amino acids that contributes significantly to the distinct sequence motifs of individual family members. When this recognition loop is grafted from the donor APOBEC3F or 3G proteins into the acceptor scaffold of AID, the mutational signature of AID changes toward that of the donor proteins. These loop-graft mutants of AID provide useful tools for dissecting the biological impact of DNA sequence preferences upon generation of antibody diversity, and the results have implications for the evolution and specialization of the AID/APOBEC family. |
| | |
Authors:
|
Rahul M Kohli; Shaun R Abrams; Kiran S Gajula; Robert W Maul; Patricia J Gearhart; James T Stivers |
Related Documents
:
|
11906807 - Predictors of internalizing and externalizing problems among children of cocaine and op... 1955217 - Filial piety and intergenerational relationship in korean immigrant families. 10169657 - Using rapid research to develop a national strategy to assist families affected by aids... 20929867 - Local sequence targeting in the aid/apobec family differentially impacts retroviral res... 20572837 - Review of recommendations for the management of dental trauma presented in first-aid te... 16737497 - From psychiatric ward to the streets and shelters. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2009-06-26 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: 284 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Aug |
Date Detail:
|
Created Date: 2009-08-17 Completed Date: 2009-10-06 Revised Date: 2010-09-24 |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 22898-904 Citation Subset: IM |
Affiliation:
|
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Motifs
/
genetics,
physiology Amino Acid Sequence Cytidine Deaminase / chemistry*, genetics, metabolism* Cytosine Deaminase / chemistry, genetics, metabolism Drug Resistance, Bacterial / genetics Enzyme Inhibitors / pharmacology Escherichia coli / drug effects, genetics Humans Molecular Sequence Data Mutation Rifampin / pharmacology Sequence Homology, Amino Acid |
| Grant Support | |
ID/Acronym/Agency:
|
GM056834-13/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Enzyme Inhibitors; 13292-46-1/Rifampin; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.1/APOBEC3F protein, human; EC 3.5.4.1/Cytosine Deaminase; EC 3.5.4.5/APOBEC3G protein, human; EC 3.5.4.5/Cytidine Deaminase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The Small Terminase, gp16, of Bacteriophage T4 Is a Regulator of the DNA Packaging Motor.
Next Document: Intersubunit coupling in the pore of BK channels.