PDBsum entry 2n4v

Transcription

PDB id: 2n4v

Contents

Protein chain

37 a.a.

PDB id:

2n4v

Name:

Transcription

Title:

Nmr structure of fbp28 ww domain t456d mutant

Structure:

Transcription elongation regulator 1. Chain: a. Synonym: tata box-binding protein-associated factor 2s, transcription factor ca150. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tcerg1, ca150, taf2s. Expressed in: escherichia coli. Expression_system_taxid: 511693.

NMR struc:

20 models

Authors:

J.Medina,M.Macias,P.Martin-Malpartida,H.A.Scheraga

Key ref:

G.G.Maisuradze et al. (2015). Preventing fibril formation of a protein by selective mutation. Proc Natl Acad Sci U S A, 112, 13549-13554. PubMed id: 26483482 DOI: 10.1073/pnas.1518298112

Date:

01-Jul-15 Release date: 21-Oct-15

Protein chain

O14776  (TCRG1_HUMAN) -  Transcription elongation regulator 1 from Homo sapiens

Seq: 1098 a.a.

Struc: 37 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.1518298112

Proc Natl Acad Sci U S A 112:13549-13554 (2015)

PubMed id: 26483482

Preventing fibril formation of a protein by selective mutation.

G.G.Maisuradze, J.Medina, K.Kachlishvili, P.Krupa, M.A.Mozolewska, P.Martin-Malpartida, L.Maisuradze, M.J.Macias, H.A.Scheraga.

ABSTRACT

The origins of formation of an intermediate state involved in amyloid formation and ways to prevent it are illustrated with the example of the Formin binding protein 28 (FBP28) WW domain, which folds with biphasic kinetics. Molecular dynamics of protein folding trajectories are used to examine local and global motions and the time dependence of formation of contacts between C(α)s and C(β)s of selected pairs of residues. Focus is placed on the WT FBP28 WW domain and its six mutants (L26D, L26E, L26W, E27Y, T29D, and T29Y), which have structures that are determined by high-resolution NMR spectroscopy. The origins of formation of an intermediate state are elucidated, viz. as formation of hairpin 1 by a hydrophobic collapse mechanism causing significant delay of formation of both hairpins, especially hairpin 2, which facilitates the emergence of an intermediate state. It seems that three-state folding is a major folding scenario for all six mutants and WT. Additionally, two-state and downhill folding scenarios were identified in ∼15% of the folding trajectories for L26D and L26W, in which both hairpins are formed by the Matheson-Scheraga mechanism much faster than in three-state folding. These results indicate that formation of hairpins connecting two antiparallel β-strands determines overall folding. The correlations between the local and global motions identified for all folding trajectories lead to the identification of the residues making the main contributions in the formation of the intermediate state. The presented findings may provide an understanding of protein folding intermediates in general and lead to a procedure for their prevention.