PDBsum entry 6kcs

DNA binding protein/DNA

PDB id: 6kcs

Contents

Protein chain

117 a.a.

DNA/RNA

Waters ×48

PDB id:

6kcs

Name:

DNA binding protein/DNA

Title:

Crystal structure of hiran domain of hltf in complex with duplex DNA

Structure:

Helicase-like transcription factor. Chain: a. Synonym: DNA-binding protein/plasminogen activator inhibitor 1 regulator,hip116,ring finger protein 80,swi/snf-related matrix- associated actin-dependent regulator of chromatin subfamily a member 3,sucrose nonfermenting protein 2-like 3. Engineered: yes. DNA (5'-d( Ap Cp Tp Gp Tp Ap Cp Gp Tp Ap Cp Ap Gp T)-3'). Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hltf, hip116a, rnf80, smarca3, snf2l3, zbu1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Resolution:

2.10Å R-factor: 0.230 R-free: 0.264

Authors:

A.Hishiki,A.Hashimoto

Key ref:

A.Hishiki et al. (2020). Structure of HIRAN domain of human HLTF bound to duplex DNA provides structural basis for DNA unwinding to initiate replication fork regression. J Biochem, 167, 597-602. PubMed id: 31960921 DOI: 10.1093/jb/mvaa008

Date:

28-Jun-19 Release date: 10-Jun-20

Protein chain

Q14527  (HLTF_HUMAN) -  Helicase-like transcription factor from Homo sapiens

Seq: 1009 a.a.

Struc: 117 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chain

T-G-T-A-C-G-T-A-C-A-G-T 12 bases

Enzyme reactions

• Enzyme class: E.C.2.3.2.27 - RING-type E3 ubiquitin transferase.
• Reaction: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N₆- ubiquitinyl-[acceptor protein]-L-lysine

DOI no: 10.1093/jb/mvaa008

J Biochem 167:597-602 (2020)

PubMed id: 31960921

Structure of HIRAN domain of human HLTF bound to duplex DNA provides structural basis for DNA unwinding to initiate replication fork regression.

A.Hishiki, M.Sato, H.Hashimoto.

ABSTRACT

Replication fork regression is a mechanism to rescue a stalled fork by various replication stresses, such as DNA lesions. Helicase-like transcription factor, a SNF2 translocase, plays a central role in the fork regression and its N-terminal domain, HIRAN (HIP116 and Rad5 N-terminal), binds the 3'-hydroxy group of single-stranded DNA. Furthermore, HIRAN is supposed to bind double-stranded DNA (dsDNA) and involved in strand separation in the fork regression, whereas structural basis for mechanisms underlying dsDNA binding and strand separation by HIRAN are still unclear. Here, we report the crystal structure of HIRAN bound to duplex DNA. The structure reveals that HIRAN binds the 3'-hydroxy group of DNA and unexpectedly unwinds three nucleobases of the duplex. Phe-142 is involved in the dsDNA binding and the strand separation. In addition, the structure unravels the mechanism underlying sequence-independent recognition for purine bases by HIRAN, where the N-glycosidic bond adopts syn conformation. Our findings indicate direct involvement of HIRAN in the fork regression by separating of the daughter strand from the parental template.