PDBsum entry 6es6

DNA binding protein

PDB id: 6es6

Contents

Protein chains

45 a.a.

50 a.a.

PDB id:

6es6

Name:

DNA binding protein

Title:

Structure and dynamics conspire in the evolution of affinity between intrinsically disordered proteins

Structure:

Cid. Chain: a. Engineered: yes. Ncbd. Chain: b. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

NMR struc:

20 models

Authors:

N.C.Chi

Key ref:

P.Jemth et al. (2018). Structure and dynamics conspire in the evolution of affinity between intrinsically disordered proteins. Sci Adv, 4, eaau4130. PubMed id: 30397651

Date:

19-Oct-17 Release date: 31-Oct-18

Protein chain

No UniProt id for this chain

Struc: 45 a.a.

Protein chain

Q92793  (CBP_HUMAN) -  CREB-binding protein from Homo sapiens

Seq: 2442 a.a.

Struc: 50 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain B: E.C.2.3.1.- - ?????
• Enzyme class 2: Chain B: E.C.2.3.1.48 - histone acetyltransferase.
• Reaction: L-lysyl-[protein] + acetyl-CoA = N₆-acetyl-L-lysyl-[protein] + CoA + H⁺

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.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Sci Adv 4:eaau4130 (2018)

PubMed id: 30397651

Structure and dynamics conspire in the evolution of affinity between intrinsically disordered proteins.

P.Jemth, E.Karlsson, B.Vögeli, B.Guzovsky, E.Andersson, G.Hultqvist, J.Dogan, P.Güntert, R.Riek, C.N.Chi.

ABSTRACT

In every established species, protein-protein interactions have evolved such that they are fit for purpose. However, the molecular details of the evolution of new protein-protein interactions are poorly understood. We have used nuclear magnetic resonance spectroscopy to investigate the changes in structure and dynamics during the evolution of a protein-protein interaction involving the intrinsically disordered CREBBP (CREB-binding protein) interaction domain (CID) and nuclear coactivator binding domain (NCBD) from the transcriptional coregulators NCOA (nuclear receptor coactivator) and CREBBP/p300, respectively. The most ancient low-affinity "Cambrian-like" [540 to 600 million years (Ma) ago] CID/NCBD complex contained less secondary structure and was more dynamic than the complexes from an evolutionarily younger "Ordovician-Silurian" fish ancestor (ca. 440 Ma ago) and extant human. The most ancient Cambrian-like CID/NCBD complex lacked one helix and several interdomain interactions, resulting in a larger solvent-accessible surface area. Furthermore, the most ancient complex had a high degree of millisecond-to-microsecond dynamics distributed along the entire sequences of both CID and NCBD. These motions were reduced in the Ordovician-Silurian CID/NCBD complex and further redistributed in the extant human CID/NCBD complex. Isothermal calorimetry experiments show that complex formation is enthalpically favorable and that affinity is modulated by a largely unfavorable entropic contribution to binding. Our data demonstrate how changes in structure and motion conspire to shape affinity during the evolution of a protein-protein complex and provide direct evidence for the role of structural, dynamic, and frustrational plasticity in the evolution of interactions between intrinsically disordered proteins.