PDBsum entry 2x7z

Structural protein

PDB id: 2x7z

Contents

Protein chain

99 a.a. *

Ligands

NH4

IMD

Waters ×82

* Residue conservation analysis

PDB id:

2x7z

Name:

Structural protein

Title:

Crystal structure of the sap97 pdz2 i342w c378a mutant protein domain

Structure:

Disks large homolog 1. Chain: a. Fragment: pdz2 domain, residues 260-356. Synonym: synapse-associated protein 97, sap97, sap-97, hdlg. Engineered: yes. Mutation: yes

Source:

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

Resolution:

2.00Å R-factor: 0.196 R-free: 0.232

Authors:

S.R.Haq,M.C.Jurgens,C.N.Chi,L.Elfstrom,C.S.Koh,M.Selmer,S.Gianni, P.Jemth

Key ref:

S.R.Haq et al. (2010). The plastic energy landscape of protein folding: a triangular folding mechanism with an equilibrium intermediate for a small protein domain. J Biol Chem, 285, 18051-18059. PubMed id: 20356847

Date:

04-Mar-10 Release date: 31-Mar-10

Protein chain

Q12959  (DLG1_HUMAN) -  Disks large homolog 1 from Homo sapiens

Seq: 904 a.a.

Struc: 99 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

J Biol Chem 285:18051-18059 (2010)

PubMed id: 20356847

The plastic energy landscape of protein folding: a triangular folding mechanism with an equilibrium intermediate for a small protein domain.

S.R.Haq, M.C.Jürgens, C.N.Chi, C.S.Koh, L.Elfström, M.Selmer, S.Gianni, P.Jemth.

ABSTRACT

Protein domains usually fold without or with only transiently populated intermediates, possibly to avoid misfolding, which could result in amyloidogenic disease. Whether observed intermediates are productive and obligatory species on the folding reaction pathway or dispensable by-products is a matter of debate. Here, we solved the crystal structure of a small protein domain, SAP97 PDZ2 I342W C378A, and determined its folding pathway. The presence of a folding intermediate was demonstrated both by single and double-mixing kinetic experiments using urea-induced (un)folding as well as ligand-induced folding. This protein domain was found to fold via a triangular scheme, where the folding intermediate could be either on- or off-pathway, depending on the experimental conditions. Furthermore, we found that the intermediate was present at equilibrium, which is rarely seen in folding reactions of small protein domains. The folding mechanism observed here illustrates the roughness and plasticity of the protein folding energy landscape, where several routes may be employed to reach the native state. The results also reconcile the folding mechanisms of topological variants within the PDZ domain family.