5A30

Crystal structure of mtPAP N472D mutant in complex with ATPgammaS

Summary for 5A30

• Entry DOI: 10.2210/pdb5a30/pdb
• Related: 5A2V 5A2W 5A2X 5A2Y 5A2Z
• Descriptor: MITOCHONDRIAL PROTEIN, MAGNESIUM ION, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: unknown function
• Biological source: GALLUS GALLUS
• Total number of polymer chains: 2
• Total formula weight: 127005.26

Authors

Lapkouski, M.,Hallberg, B.M. (deposition date: 2015-05-26, release date: 2015-09-09, Last modification date: 2024-05-08)

Primary citation

Lapkouski, M.,Hallberg, B.M.
Structure of Mitochondrial Poly(A) RNA Polymerase Reveals the Structural Basis for Dimerization, ATP Selectivity and the Spax4 Disease Phenotype.
Nucleic Acids Res., 43:9065-, 2015

PubMed Abstract: Polyadenylation, performed by poly(A) polymerases (PAPs), is a ubiquitous post-transcriptional modification that plays key roles in multiple aspects of RNA metabolism. Although cytoplasmic and nuclear PAPs have been studied extensively, the mechanism by which mitochondrial PAP (mtPAP) selects adenosine triphosphate over other nucleotides is unknown. Furthermore, mtPAP is unique because it acts as a dimer. However, mtPAP's dimerization requirement remains enigmatic. Here, we show the structural basis for mtPAP's nucleotide selectivity, dimerization and catalysis. Our structures reveal an intricate dimerization interface that features an RNA-recognition module formed through strand complementation. Further, we propose the structural basis for the N478D mutation that drastically reduces the length of poly(A) tails on mitochondrial mRNAs in patients with spastic ataxia 4 (SPAX4), a severe and progressive neurodegenerative disease.

PubMed: 26319014
DOI: 10.1093/NAR/GKV861

Experimental method

X-RAY DIFFRACTION (2.75 Å)