Modomics - A Database of RNA Modifications

ID Card:

Full name: Single-stranded DNA cytosine deaminase
Synonym: AID
GI: 23813666
UniProt: Q9GZX7
Structures: | 5JJ4 | 5W0R | 5W0U | 5W0Z | 5W1C |
Alpha Fold Predicted Structure: AF-Q9GZX7-F1
Enzyme type: deaminase


PDB Structures:


5JJ4

Structure Description:

Title: Crystal Structure of a Variant Human Activation-induced Deoxycytidine Deaminase as an MBP fusion protein
Classification: HYDROLASE
Technique: X-Ray Diffraction
Resolution: 2.81
R value free: 0.232
R value observed: 0.185
R value work: 0.183

Abstract of the PDB Structure's related Publication:

Activation-induced deoxycytidine deaminase (AID) initiates somatic hypermutation (SHM) and class-switch recombination (CSR) by deaminating C→U during transcription of Ig-variable (V) and Ig-switch (S) region DNA, which is essential to produce high-affinity antibodies. Here we report the crystal structure of a soluble human AID variant at 2.8Å resolution that favors targeting WRC motifs (W=A/T, R=A/G) in vitro, and executes Ig V SHM in Ramos B-cells. A specificity loop extending away from the active site to accommodate two purine bases next to C, differs significantly in sequence, length, and conformation from APOBEC proteins Apo3A and Apo3G, which strongly favor pyrimidines at -1 and -2 positions. Individual amino acid contributions to specificity and processivity were measured in relation to a proposed ssDNA binding cleft. This study provides a structural basis for residue contributions to DNA scanning properties unique to AID, and for disease mutations in human HIGM-2 syndrome.

Download RCSB-PDB Structures:

Pdb Files   5JJ4.pdb   5W0R.pdb   5W0U.pdb   5W0Z.pdb   5W1C.pdb  
Pdbx/mmCIF Files   5JJ4.cif   5W0R.cif   5W0U.cif   5W0Z.cif   5W1C.cif  


Protein sequence:

MDSLLMNRRKFLYQFKNVRWAKGRRETYLCYVVKRRDSATSFSLDFGYLRNKNGCHVELLFLRYISDWDLDPGRCYRVTWFTSWSPCYDCARHVADFLRGNPNLSLRIFTARLYFCEDRKAEPEGLRRLHRAGVQIAIMTFKENHERTFKAWEGLHENSVRLSRQLRRILLPLYEVDDLRDAFRTLGL

Comments:

Activation Induced cytidine Deaminase belongs to the mammalian enzyme family known as the "activation-induced deaminase/apolipoprotein B-mRNA-editing enzyme catalytic polypeptide like" (AID/APOBEC) protein family. AID/APOBEC share three major common elements, ultimately displaying a conserved protein architecture (Pecori et al. 2022 ).

They comprise the catalytic domain that contains an enzymatic pocket that partially overlpas with the substrate binding surface (Pecori et al. 2022 ).

Some of these enzymes have a cofactor interacting region and certain sequene elements that define their subcellular localization (Pecori et al. 2022 ).AID can both deaminate RNA and ssDNA, as well. However, no RNA modification has been observed so far. AID expression (Pecori et al. 2022 ). AID expression is regulated both transcriptionally and post-transcriptionally.

MicroRNAs (miR-155, miR-181b, miR-361, and miR-93) have a major role in AID suppression, targeting 3'-UTR (Takai et al. 2015).

AID preferentially deaminates DNA cytidine in the 5'-WRC-3' sequence context (W=dA/dT, R=dC/dG). AID catalyzes deamination within variable antibody region V(D)J gene segments of Immunoglobuline (Ig) genes in B cells, leading to somatic hypermutations (SHM). It also targets repetitive 'switch' regions leading to class switch recombination (Takai et al. 2015).

Post-translational modifications are essential for AID activity to be performed. Phosphorylation is indeed important for modulating AID's activity in B cells, where AID is phosphorylated on serine 38 (Ser38) (Takai et al. 2015).





Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

M D S L L M N R R K F L Y Q F K N V R W A K G R R E T Y L C Y V V K R R D S A T S F S L D F G Y L R N K N G C H V E L L F L R Y I S D W D L D P G R C Y R V T W F T S W S P C Y D C A R H V A D F L R G N P N L S L R I F T A R L Y F C E D R K A E P E G L R R L H R A G V Q I A I M T F K E N H E R T F K A W E G L H E N S V R L S R Q L R R I L L P L Y E V D D L R D A F R T L G L
20406080100120140160180MDSLLMNRRKFLYQFKNVRWAKGRRETYLCYVVKRRDSATSFSLDFGYLRNKNGCHVELLFLRYISDWDLDPGRCYRVTWFTSWSPCYDCARHVADFLRGNPNLSLRIFTARLYFCEDRKAEPEGLRRLHRAGVQIAIMTFKENHERTFKAWEGLHENSVRLSRQLRRILLPLYEVDDLRDAFRTLGLSequenceHTBSN

Enter the variants

Position

Original

Variant

Secondary Structure Alphabet

  • G: 3-turn helix (310helix)
  • H: α-helix
  • I: 𝝅-helix (5 - turn helix)
  • T: Hydrogen Bonded Turn
  • B: β-sheet
  • S: Bend
  • C: Coil (residues not present in any of the above conformations)
  • N: Not assigned

Download PDB Structures & DSSP Secondary Structures:

Alpha Fold Pdb Files   AF-Q9GZX7-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q9GZX7-F1.cif  
DSSP Secondary Structures   Q9GZX7.dssp  





Publications: