PDBsum entry 6ej5

RNA binding protein

PDB id: 6ej5

Contents

Protein chain

599 a.a.

Waters ×3

PDB id:

6ej5

Name:

RNA binding protein

Title:

A conserved structural element in the RNA helicase upf1 regulates its catalytic activity in an isoform-specific manner

Structure:

Regulator of nonsense transcripts 1. Chain: a. Synonym: atp-dependent helicase rent1,nonsense mRNA reducing factor 1,norf1,up-frameshift suppressor 1 homolog,hupf1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: upf1, kiaa0221, rent1. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

3.34Å R-factor: 0.286 R-free: 0.309

Authors:

M.Gowravaram,F.Bonneau,V.D.Maciej,S.Chakrabarti

Key ref:

M.Gowravaram et al. (2018). A conserved structural element in the RNA helicase UPF1 regulates its catalytic activity in an isoform-specific manner. Nucleic Acids Res, 46, 2648-2659. PubMed id: 29378013

Date:

20-Sep-17 Release date: 24-Jan-18

Protein chain

Q92900  (RENT1_HUMAN) -  Regulator of nonsense transcripts 1 from Homo sapiens

Seq: 1129 a.a.

Struc: 599 a.a.*

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

Enzyme reactions

• Enzyme class 2: E.C.3.6.4.12 - Dna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺
• Enzyme class 3: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Nucleic Acids Res 46:2648-2659 (2018)

PubMed id: 29378013

A conserved structural element in the RNA helicase UPF1 regulates its catalytic activity in an isoform-specific manner.

M.Gowravaram, F.Bonneau, J.Kanaan, V.D.Maciej, F.Fiorini, S.Raj, V.Croquette, H.Le Hir, S.Chakrabarti.

ABSTRACT

The RNA helicase UPF1 is a key component of the nonsense mediated mRNA decay (NMD) pathway. Previous X-ray crystal structures of UPF1 elucidated the molecular mechanisms of its catalytic activity and regulation. In this study, we examine features of the UPF1 core and identify a structural element that adopts different conformations in the various nucleotide- and RNA-bound states of UPF1. We demonstrate, using biochemical and single molecule assays, that this structural element modulates UPF1 catalytic activity and thereby refer to it as the regulatory loop. Interestingly, there are two alternatively spliced isoforms of UPF1 in mammals which differ only in the lengths of their regulatory loops. The loop in isoform 1 (UPF11) is 11 residues longer than that of isoform 2. We find that this small insertion in UPF11 leads to a two-fold increase in its translocation and ATPase activities. To determine the mechanistic basis of this differential catalytic activity, we have determined the X-ray crystal structure of the helicase core of UPF11 in its apo-state. Our results point toward a novel mechanism of regulation of RNA helicases, wherein alternative splicing leads to subtle structural rearrangements within the protein that are critical to modulate enzyme movements and catalytic activity.