Modomics - A Database of RNA Modifications

ID Card:

Full name: rRNA N6-adenosine-methyltransferase
GI: 85700439
UniProt: Q9H5U6
Structures: | 6UCA |
Alpha Fold Predicted Structure: AF-Q9H5U6-F1
Complex: None
Enzyme type: methyltransferase


PDB Structures:


6UCA

Structure Description:

Title:
Classification:
Technique:

Abstract of the PDB Structure's related Publication:

N 6 -methyladenosine (m 6 A) modification provides an important epitranscriptomic mechanism that critically regulates RNA metabolism and function. However, how m 6 A writers attain substrate specificities remains unclear. We report the 3.1 Å-resolution crystal structure of human CCHC zinc finger-containing protein ZCCHC4, a 28S rRNA-specific m 6 A methyltransferase, bound to S-adenosyl-L-homocysteine. The methyltransferase (MTase) domain of ZCCHC4 is packed against N-terminal GRF-type and C2H2 zinc finger domains and a C-terminal CCHC domain, creating an integrated RNA-binding surface. Strikingly, the MTase domain adopts an autoinhibitory conformation, with a self-occluded catalytic site and a fully-closed cofactor pocket. Mutational and enzymatic analyses further substantiate the molecular basis for ZCCHC4-RNA recognition and a role of the stem-loop structure within substrate in governing the substrate specificity. Overall, this study unveils unique structural and enzymatic characteristics of ZCCHC4, distinctive from what was seen with the METTL family of m 6 A writers, providing the mechanistic basis for ZCCHC4 modulation of m 6 A RNA methylation.

Download RCSB-PDB Structures:

Pdb Files   6UCA.pdb  
Pdbx/mmCIF Files   6UCA.cif  


Protein sequence:

MAASRNGFEAVEAEGSAGCRGSSGMEVVLPLDPAVPAPLCPHGPTLLFVKVTQGKEETRRFYACSACRDRKDCNFFQWEDEKLSGARLAAREAHNRRCQPPLSRTQCVERYLKFIELPLTQRKFCQTCQQLLLPDDWGQHSEHQVLGNVSITQLRRPSQLLYPLENKKTNAQYLFADRSCQFLVDLLSALGFRRVLCVGTPRLHELIKLTASGDKKSNIKSLLLDIDFRYSQFYMEDSFCHYNMFNHHFFDGKTALEVCRAFLQEDKGEGIIMVTDPPFGGLVEPLAITFKKLIAMWKEGQSQDDSHKELPIFWIFPYFFESRICQFFPSFQMLDYQVDYDNHALYKHGKTGRKQSPVRIFTNIPPNKIILPTEEGYRFCSPCQRYVSLENQHCELCNSCTSKDGRKWNHCFLCKKCVKPSWIHCSICNHCAVPDHSCEGPKHGCFICGELDHKRSTCPNIATSKRANKAVRKQKQRKSNKMKMETTKGQSMNHTSATRRKKRRERAHQYLGS

Comments:

rRNA N6-methyltransferase that specifically methylates the adenine in position 4220 of 28S rRNA. N6-methylation of adenine(4220) in 28S rRNA is required for translation





Alpha Fold Predicted Structure:






Clear Selection and Reset Camera

Protein sequence:

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

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-Q9H5U6-F1.pdb  
Alpha Fold Pdbx/mmCIF Files   AF-Q9H5U6-F1.cif  
DSSP Secondary Structures   Q9H5U6.dssp  





Publications:

Title Authors Journal Details PubMed Id DOI
The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112. Nhan van Tran,Felix G M Ernst,Ben R Hawley,Christiane Zorbas,Nathalie Ulryck,Philipp Hackert,Katherine E Bohnsack,Markus T Bohnsack,Samie R Jaffrey,Marc Graille,Denis L J Lafontaine Nucleic Acids Res [details] 31328227 -
NMethyladenosine methyltransferase ZCCHC4 mediates ribosomal RNA methylation. Honghui Ma,Xiaoyun Wang,Jiabin Cai,Qing Dai,S Kundhavai Natchiar,Ruitu Lv,Kai Chen,Zhike Lu,Hao Chen,Yujiang Geno Shi,Fei Lan,Jia Fan,Bruno P Klaholz,Tao Pan,Yang Shi,Chuan He Nat Chem Biol [details] 30531910 -
The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA. Rita Pinto,Cathrine B Vågbø,Magnus E Jakobsson,Yeji Kim,Marijke P Baltissen,Marie-Françoise O'Donohue,Ulises H Guzmán,Jędrzej M Małecki,Jie Wu,Finn Kirpekar,Jesper V Olsen,Pierre-Emmanuel Gleizes,Michiel Vermeulen,Sebastian A Leidel,Geir Slupphaug,Pål Ø Falnes Nucleic Acids Res [details] 31799605 -
Structure and regulation of ZCCHC4 in mA-methylation of 28S rRNA. Wendan Ren,Jiuwei Lu,Mengjiang Huang,Linfeng Gao,Dongxu Li,Gang Greg Wang,Jikui Song Nat Commun [details] 31695039 -