PDBsum entry 1i0c

Hormone/growth factor

PDB id: 1i0c

Contents

Protein chains

59 a.a. *

Waters ×92

* Residue conservation analysis

PDB id:

1i0c

Name:

Hormone/growth factor

Title:

Eps8 sh3 closed monomer

Structure:

Epidermal growth factor receptor kinase substrate eps8. Chain: a, b. Fragment: sh3 domain. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.189 R-free: 0.235

Authors:

K.V.R.Kishan,M.E.Newcomer

Key ref:

K.V.Kishan et al. (2001). Effect of pH and salt bridges on structural assembly: molecular structures of the monomer and intertwined dimer of the Eps8 SH3 domain. Protein Sci, 10, 1046-1055. PubMed id: 11316885

Date:

29-Jan-01 Release date: 09-May-01

Protein chains

Q08509  (EPS8_MOUSE) -  Epidermal growth factor receptor kinase substrate 8 from Mus musculus

Seq: 821 a.a.

Struc: 59 a.a.

Enzyme reactions

• Enzyme class: E.C.?

Protein Sci 10:1046-1055 (2001)

PubMed id: 11316885

Effect of pH and salt bridges on structural assembly: molecular structures of the monomer and intertwined dimer of the Eps8 SH3 domain.

K.V.Kishan, M.E.Newcomer, T.H.Rhodes, S.D.Guilliot.

ABSTRACT

The SH3 domain of Eps8 was previously found to form an intertwined, domain-swapped dimer. We report here a monomeric structure of the EPS8 SH3 domain obtained from crystals grown at low pH, as well as an improved domain-swapped dimer structure at 1.8 A resolution. In the domain-swapped dimer the asymmetric unit contains two "hybrid-monomers." In the low pH form there are two independently folded SH3 molecules per asymmetric unit. The formation of intermolecular salt bridges is thought to be the reason for the formation of the dimer. On the basis of the monomer SH3 structure, it is argued that Eps8 SH3 should, in principle, bind to peptides containing a PxxP motif. Recently it was reported that Eps8 SH3 binds to a peptide with a PxxDY motif. Because the "SH3 fold" is conserved, alternate binding sites may be possible for the PxxDY motif to bind. The strand exchange or domain swap occurs at the n-src loops because the n-src loops are flexible. The thermal b-factors also indicate the flexible nature of n-src loops and a possible handle for domain swap initiation. Despite the loop swapping, the typical SH3 fold in both forms is conserved structurally. The interface of the acidic form of SH3 is stabilized by a tetragonal network of water molecules above hydrophobic residues. The intertwined dimer interface is stabilized by hydrophobic and aromatic stacking interactions in the core and by hydrophilic interactions on the surface.