PDBsum entry 3zlz

Signaling protein

PDB id: 3zlz

Contents

Protein chains

73 a.a.

Metals

_ZN ×5

PDB id:

3zlz

Name:

Signaling protein

Title:

Lys6-linked tri-ubiquitin

Structure:

Ubiquitin. Chain: a, b. Engineered: yes. Mutation: yes. Other_details: tri-ubiquitin chain linked via lys6. K48r in both molecules. Isopeptide linkages are not resolved.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta2 placi.

Resolution:

2.90Å R-factor: 0.254 R-free: 0.288

Authors:

M.K.Hospenthal,S.M.V.Freund,D.Komander

Key ref:

M.K.Hospenthal et al. (2013). Assembly, analysis and architecture of atypical ubiquitin chains. Nat Struct Biol, 20, 555-565. PubMed id: 23563141 DOI: 10.1038/nsmb.2547

Date:

04-Feb-13 Release date: 10-Apr-13

Protein chains

P0CG47  (UBB_HUMAN) -  Polyubiquitin-B from Homo sapiens

Seq: 229 a.a.

Struc: 73 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nsmb.2547

Nat Struct Biol 20:555-565 (2013)

PubMed id: 23563141

Assembly, analysis and architecture of atypical ubiquitin chains.

M.K.Hospenthal, S.M.Freund, D.Komander.

ABSTRACT

Ubiquitin (Ub) chains regulate many cellular processes, but several chain types including Lys6 linkages have remained unstudied. Here we analyze the bacterial effector E3 ligase NleL (non-Lee-encoded effector ligase) from enterohemorrhagic Escherichia coli (EHEC) O157:H7, which assembles Lys6- and Lys48-linked Ub polymers. Using linkage-specific human deubiquitinases (DUBs) we show that NleL generates heterotypic Ub chains, and branched chains are efficiently hydrolyzed by DUBs. USP family DUBs cleave Lys6-linked polymers exclusively from the distal end, whereas a DUB with preference for Lys6 can cleave Lys6-linked polymers at any position in the chain. We used NleL to generate large quantities of Lys6-linked polyUb. Crystallographic and NMR spectroscopy analyses revealed that an asymmetric interface between Ile44 and Ile36 hydrophobic patches of neighboring Ub moieties is propagated in longer Lys6-linked Ub chains. Interactions via the Ile36 patch can displace Leu8 from the Ile44 patch, leading to marked structural perturbations of Ub.