PDBsum entry 2k8c

Protein binding

PDB id: 2k8c

Contents

Protein chains

76 a.a. *

80 a.a. *

* Residue conservation analysis

PDB id:

2k8c

Name:

Protein binding

Title:

Solution structure of plaa family ubiquitin binding domain (pfuc) trans isomer in complex with ubiquitin

Structure:

Ubiquitin. Chain: a. Engineered: yes. Phospholipase a-2-activating protein. Chain: b. Fragment: unp residues 386-465. Synonym: pla2p, plap. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rps27a, uba80, ubcep1, uba52, ubcep2, ubb, ubc. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: plaa, plap.

NMR struc:

10 models

Authors:

Q.S.Fu,C.J.Zhou,H.C.Gao,D.H.Lin,H.Y.Hu

Key ref:

Q.S.Fu et al. (2009). Structural Basis for Ubiquitin Recognition by a Novel Domain from Human Phospholipase A2-activating Protein. J Biol Chem, 284, 19043-19052. PubMed id: 19423704 DOI: 10.1074/jbc.M109.009126

Date:

04-Sep-08 Release date: 05-May-09

Protein chain

P0CG48  (UBC_HUMAN) -  Polyubiquitin-C from Homo sapiens

Seq: 685 a.a.

Struc: 76 a.a.

Protein chain

Q9Y263  (PLAP_HUMAN) -  Phospholipase A-2-activating protein from Homo sapiens

Seq: 795 a.a.

Struc: 80 a.a.

DOI no: 10.1074/jbc.M109.009126

J Biol Chem 284:19043-19052 (2009)

PubMed id: 19423704

Structural Basis for Ubiquitin Recognition by a Novel Domain from Human Phospholipase A2-activating Protein.

Q.S.Fu, C.J.Zhou, H.C.Gao, Y.J.Jiang, Z.R.Zhou, J.Hong, W.M.Yao, A.X.Song, D.H.Lin, H.Y.Hu.

ABSTRACT

Ubiquitin (Ub) is an essential modifier conserved in all eukaryotes from yeast to human. Phospholipase A(2)-activating protein (PLAA), a mammalian homolog of yeast DOA1/UFD3, has been proposed to be able to bind with Ub, which plays important roles in endoplasmic reticulum-associated degradation, vesicle formation, and DNA damage response. We have identified a core domain from the PLAA family ubiquitin-binding region of human PLAA (residues 386-465, namely PFUC) that can bind Ub and elucidated its solution structure and Ub-binding mode by NMR approaches. The PFUC domain possesses equal population of two conformers in solution by cis/trans-isomerization, whereas the two isomers exhibit almost equivalent Ub binding abilities. This domain structure takes a novel fold consisting of four beta-strands and two alpha-helices, and the Ub-binding site on PFUC locates in the surface of alpha2-helix, which is to some extent analogous to those of UBA, CUE, and UIM domains. This study provides structural basis and biochemical information for Ub recognition of the novel PFU domain from a PLAA family protein that may connect ubiquitination and degradation in endoplasmic reticulum-associated degradation.

Selected figure(s)

Figure 4.
Solution structure of the PFUC domain. A, backbone superposition of 15 lowest-energy structures in cis (left panel) and trans (right panel) isomers. B, ribbon representation of the structures for cis (left panel) and trans (right panel) isomers. N and C indicate the N and C termini of PFUC, respectively. C, comparison of the cis and trans isomers in the loop between β3 and β4 where Pro^77 resides. The Gly^76–Pro^77 prolyl bonds in both cis- and trans-isomers are fit together and the side chain positions of Gly^76 and Pro^77 are shown in red (cis) and blue (trans).

Figure 5.
HADDOCK-derived model for the PFUC-Ub complex. A, backbone superposition of 10 refined cis-PFUC-Ub complex structures. The average energy for the cluster is −6349 ± 59 kcal·mol^−1 for the cis-PFUC-Ub complex and that is −6377 ± 81 kcal·mol^−1 for trans-PFUC-Ub. The root mean square deviation of all backbone atoms in the interfaces is 1.2 ± 0.8 Å for cis-PFUC-Ub and 1.1 ± 0.9 Å for trans-PFUC-Ub. B, close-up view of the interfaces showing the side chains of key interacting residues. The stick representations are in red for the side chains from Ub and in blue for those from PFUC.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 19043-19052) copyright 2009.

Figures were selected by the author.