PDBsum entry 6b0b

Hydrolase/RNA

PDB id: 6b0b

Contents

Protein chains

180 a.a.

205 a.a.

DNA/RNA

Metals

_ZN ×2

Waters ×2

PDB id:

6b0b

Name:

Hydrolase/RNA

Title:

Crystal structure of human apobec3h

Structure:

Apobec3h. Chain: a, e. Engineered: yes. RNA (5'-r( Up Ap Ap Ap Ap Ap Ap A)-3'). Chain: b, f. RNA (5'-r( Up Up Up Up Up Up Up U)-3'). Chain: c, g. Mcherry. Chain: d, h.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: apobec3h. Expressed in: escherichia coli. Expression_system_taxid: 562. Escherichia coli. Organism_taxid: 562. Discosoma sp..

Resolution:

3.28Å R-factor: 0.353 R-free: 0.362

Authors:

N.M.Shaban,K.Shi,S.Banerjee,R.S.Harris,H.Aihara

Key ref:

N.M.Shaban et al. (2018). The Antiviral and Cancer Genomic DNA Deaminase APOBEC3H Is Regulated by an RNA-Mediated Dimerization Mechanism. Mol Cell, 69, 75. PubMed id: 29290613 DOI: 10.1016/j.molcel.2017.12.010

Date:

14-Sep-17 Release date: 25-Oct-17

Protein chains

Q6NTF7  (ABC3H_HUMAN) -  DNA dC->dU-editing enzyme APOBEC-3H from Homo sapiens

Seq: 200 a.a.

Struc: 180 a.a.*

Protein chains

D1MPT3  (D1MPT3_DISSP) -  PAmCherry1 protein from Discosoma sp.

Seq: 236 a.a.

Struc: 205 a.a.*

* PDB and UniProt seqs differ at 15 residue positions (black crosses)

DNA/RNA chains

U-A-A-A-A-A-A-A 8 bases

U-U-U-U-U-U-U-U 8 bases

U-A-A-A-A-A-A-A 8 bases

U-U-U-U-U-U-U-U 8 bases

Enzyme reactions

• Enzyme class: Chains A, E: E.C.3.5.4.38 - single-stranded Dna cytosine deaminase.
• Reaction: a 2'-deoxycytidine in single-stranded DNA + H2O + H⁺ = a 2'-deoxyuridine in single-stranded DNA + NH4⁺

DOI no: 10.1016/j.molcel.2017.12.010

Mol Cell 69:75 (2018)

PubMed id: 29290613

The Antiviral and Cancer Genomic DNA Deaminase APOBEC3H Is Regulated by an RNA-Mediated Dimerization Mechanism.

N.M.Shaban, K.Shi, K.V.Lauer, M.A.Carpenter, C.M.Richards, D.Salamango, J.Wang, M.W.Lopresti, S.Banerjee, R.Levin-Klein, W.L.Brown, H.Aihara, R.S.Harris.

ABSTRACT

Human APOBEC3H and homologous single-stranded DNA cytosine deaminases are unique to mammals. These DNA-editing enzymes function in innate immunity by restricting the replication of viruses and transposons. APOBEC3H also contributes to cancer mutagenesis. Here, we address the fundamental nature of RNA in regulating human APOBEC3H activities. APOBEC3H co-purifies with RNA as an inactive protein, and RNase A treatment enables strong DNA deaminase activity. RNA-binding-defective mutants demonstrate clear separation of function by becoming DNA hypermutators. Biochemical and crystallographic data demonstrate a mechanism in which double-stranded RNA mediates enzyme dimerization. Additionally, APOBEC3H separation-of-function mutants show that RNA binding is required for cytoplasmic localization, packaging into HIV-1 particles, and antiviral activity. Overall, these results support a model in which structured RNA negatively regulates the potentially harmful DNA deamination activity of APOBEC3H while, at the same time, positively regulating its antiviral activity.