3ZLZ

Lys6-linked tri-ubiquitin

Summary for 3ZLZ

• Entry DOI: 10.2210/pdb3zlz/pdb
• Descriptor: UBIQUITIN, ZINC ION (2 entities in total)
• Functional Keywords: signaling protein, atypical chain type, deubiquitinase, nlel, bacterial effector
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Ubiquitin: Cytoplasm : P0CG47
• Total number of polymer chains: 2
• Total formula weight: 17536.73

Authors

Hospenthal, M.K.,Freund, S.M.V.,Komander, D. (deposition date: 2013-02-04, release date: 2013-04-10, Last modification date: 2023-12-20)

Primary citation

Hospenthal, M.K.,Freund, S.M.V.,Komander, D.
Assembly, Analysis and Architecture of Atypical Ubiquitin Chains
Nat.Struct.Mol.Biol., 20:555-, 2013

PubMed 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.

PubMed: 23563141
DOI: 10.1038/NSMB.2547

Experimental method

X-RAY DIFFRACTION (2.9 Å)