PDBsum entry 5hfc

Peptide binding protein

PDB id: 5hfc

Contents

Protein chain

117 a.a.

Ligands

ASN-TYR-LYS-GLN-PHE-SER-VAL

Waters ×124

PDB id:

5hfc

Name:

Peptide binding protein

Title:

The third pdz domain from the synaptic protein psd-95 (h372a mutant) in complex with a mutant c-terminal peptide derived from cript (t-2f)

Structure:

Disks large homolog 4. Chain: a. Fragment: pdz-3 domain (unp residues 302-402). Synonym: postsynaptic density protein 95,psd-95,synapse-associated protein 90,sap90. Engineered: yes. Mutation: yes. Cysteine-rich pdz-binding protein. Chain: b.

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: dlg4, dlgh4, psd95. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 10116

Resolution:

1.85Å R-factor: 0.187 R-free: 0.207

Authors:

K.I.White,A.S.Raman,R.Ranganathan

Key ref:

A.S.Raman et al. (2016). Origins of Allostery and Evolvability in Proteins: A Case Study. Cell, 166, 468-480. PubMed id: 27321669 DOI: 10.1016/j.cell.2016.05.047

Date:

06-Jan-16 Release date: 16-Nov-16

Protein chain

P31016  (DLG4_RAT) -  Disks large homolog 4 from Rattus norvegicus

Seq: 724 a.a.

Struc: 117 a.a.*

* PDB and UniProt seqs differ at 17 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.cell.2016.05.047

Cell 166:468-480 (2016)

PubMed id: 27321669

Origins of Allostery and Evolvability in Proteins: A Case Study.

A.S.Raman, K.I.White, R.Ranganathan.

ABSTRACT

Proteins display the capacity for adaptation to new functions, a property critical for evolvability. But what structural principles underlie the capacity for adaptation? Here, we show that adaptation to a physiologically distinct class of ligand specificity in a PSD95, DLG1, ZO-1 (PDZ) domain preferentially occurs through class-bridging intermediate mutations located distant from the ligand-binding site. These mutations provide a functional link between ligand classes and demonstrate the principle of "conditional neutrality" in mediating evolutionary adaptation. Structures show that class-bridging mutations work allosterically to open up conformational plasticity at the active site, permitting novel functions while retaining existing function. More generally, the class-bridging phenotype arises from mutations in an evolutionarily conserved network of coevolving amino acids in the PDZ family (the sector) that connects the active site to distant surface sites. These findings introduce the concept that allostery in proteins could have its origins not in protein function but in the capacity to adapt.