PDBsum entry 2m3o

Peptide binding protein/protein binding

PDB id: 2m3o

Contents

Protein chains

43 a.a.

11 a.a.

PDB id:

2m3o

Name:

Peptide binding protein/protein binding

Title:

Structure and dynamics of a human nedd4 ww domain-enac complex

Structure:

E3 ubiquitin-protein ligase nedd4. Chain: w. Fragment: third ww domain. Synonym: cell proliferation-inducing gene 53 protein, neural precursor cell expressed developmentally down-regulated protein 4, nedd-4. Engineered: yes. Amiloride-sensitive sodium channel subunit alpha. Chain: p.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nedd4, kiaa0093, nedd4-1, pig53. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

NMR struc:

15 models

Authors:

R.Bobby,K.Medini,P.Neudecker,V.Lee,F.J.Macdonald,M.A.Brimble,J.Lott, A.J.Dingley

Key ref:

R.Bobby et al. (2013). Structure and dynamics of human Nedd4-1 WW3 in complex with the αENaC PY motif. Biochim Biophys Acta, 1834, 1632-1641. PubMed id: 23665454 DOI: 10.1016/j.bbapap.2013.04.031

Date:

23-Jan-13 Release date: 28-Aug-13

Protein chain

P46934  (NEDD4_HUMAN) -  E3 ubiquitin-protein ligase NEDD4 from Homo sapiens

Seq: 1319 a.a.

Struc: 43 a.a.*

Protein chain

P37088  (SCNNA_HUMAN) -  Amiloride-sensitive sodium channel subunit alpha from Homo sapiens

Seq: 669 a.a.

Struc: 11 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chain P: E.C.?
• Enzyme class 3: Chain W: E.C.2.3.2.26 - HECT-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

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.

DOI no: 10.1016/j.bbapap.2013.04.031

Biochim Biophys Acta 1834:1632-1641 (2013)

PubMed id: 23665454

Structure and dynamics of human Nedd4-1 WW3 in complex with the αENaC PY motif.

R.Bobby, K.Medini, P.Neudecker, T.V.Lee, M.A.Brimble, F.J.McDonald, J.S.Lott, A.J.Dingley.

ABSTRACT

Nedd4-1 (neuronal precursor cell expressed developmentally downregulated gene 4-1) is an E3 ubiquitin ligase that interacts with and negatively regulates the epithelial Na(+) channel (ENaC). The WW domains of Nedd4-1 bind to the ENaC subunits via recognition of PY motifs. Human Nedd4-1 (hNedd4-1) contains four WW domains with the third domain (WW3*) showing the strongest affinity to the PY motif. To understand the mechanism underlying this binding affinity, we have carried out NMR structural and dynamics analyses of the hNedd4-1 WW3* domain in complex with a peptide comprising the C-terminal tail of the human ENaC α-subunit. The structure reveals that the peptide interacts in a similar manner to other WW domain-ENaC peptide structures. Crucial interactions that likely provide binding affinity are the broad XP groove facilitating additional contacts between the WW3* domain and the peptide, compared to similar complexes, and the large surface area buried (83Å(2)) between R430 (WW3*) and L647' (αENaC). This corroborates the model-free analysis of the (15)N backbone relaxation data, which showed that R430 is the most rigid residue in the domain (S(2)=0.90±0.01). Carr-Purcell-Meiboom-Gill relaxation dispersion analysis identified two different conformational exchange processes on the μs-ms time-scale. One of these processes involves residues located at the peptide binding interface, suggesting conformational exchange may play a role in peptide recognition. Thus, both structural and dynamic features of the complex appear to define the high binding affinity. The results should aid interpretation of biochemical data and modeling interfaces between Nedd4-1 and other interacting proteins.