PDBsum entry 2m8i

Isomerase

PDB id: 2m8i

Contents

Protein chain

43 a.a.

PDB id:

2m8i

Name:

Isomerase

Title:

Structure of pin1 ww domain

Structure:

Peptidyl-prolyl cis-trans isomerase nima-interacting 1. Chain: a. Synonym: peptidyl-prolyl cis-trans isomerase pin1, ppiase pin1, rotamase pin1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pin1. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

L.M.Luh,D.K.Kirchner,F.Loehr,R.Haensel,V.Doetsch

Key ref:

L.M.Luh et al. (2013). Molecular crowding drives active Pin1 into nonspecific complexes with endogenous proteins prior to substrate recognition. J Am Chem Soc, 135, 13796-13803. PubMed id: 23968199 DOI: 10.1021/ja405244v

Date:

22-May-13 Release date: 09-Apr-14

Protein chain

Q13526  (PIN1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 from Homo sapiens

Seq: 163 a.a.

Struc: 43 a.a.

Enzyme reactions

• Enzyme class: E.C.5.2.1.8 - peptidylprolyl isomerase.
• Reaction: [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)

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

Added reference

DOI no: 10.1021/ja405244v

J Am Chem Soc 135:13796-13803 (2013)

PubMed id: 23968199

Molecular crowding drives active Pin1 into nonspecific complexes with endogenous proteins prior to substrate recognition.

L.M.Luh, R.Hänsel, F.Löhr, D.K.Kirchner, K.Krauskopf, S.Pitzius, B.Schäfer, P.Tufar, I.Corbeski, P.Güntert, V.Dötsch.

ABSTRACT

Proteins and nucleic acids maintain the crowded interior of a living cell and can reach concentrations in the order of 200-400 g/L which affects the physicochemical parameters of the environment, such as viscosity and hydrodynamic as well as nonspecific strong repulsive and weak attractive interactions. Dynamics, structure, and activity of macromolecules were demonstrated to be affected by these parameters. However, it remains controversially debated, which of these factors are the dominant cause for the observed alterations in vivo. In this study we investigated the globular folded peptidyl-prolyl isomerase Pin1 in Xenopus laevis oocytes and in native-like crowded oocyte extract by in-cell NMR spectroscopy. We show that active Pin1 is driven into nonspecific weak attractive interactions with intracellular proteins prior to substrate recognition. The substrate recognition site of Pin1 performs specific and nonspecific attractive interactions. Phosphorylation of the WW domain at Ser16 by PKA abrogates both substrate recognition and the nonspecific interactions with the endogenous proteins. Our results validate the hypothesis formulated by McConkey that the majority of globular folded proteins with surface charge properties close to neutral under physiological conditions reside in macromolecular complexes with other sticky proteins due to molecular crowding. In addition, we demonstrate that commonly used synthetic crowding agents like Ficoll 70 are not suitable to mimic the intracellular environment due to their incapability to simulate biologically important weak attractive interactions.