5LO3

Engineering protein stability with atomic precision in a monomeric miniprotein


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Submitted: 20 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Engineering protein stability with atomic precision in a monomeric miniprotein.

Baker, E.G.Williams, C.Hudson, K.L.Bartlett, G.J.Heal, J.W.Porter Goff, K.L.Sessions, R.B.Crump, M.P.Woolfson, D.N.

(2017) Nat Chem Biol 13: 764-770

  • DOI: https://doi.org/10.1038/nchembio.2380
  • Primary Citation of Related Structures:  
    5LO2, 5LO3, 5LO4

  • PubMed Abstract: 

    Miniproteins simplify the protein-folding problem, allowing the dissection of forces that stabilize protein structures. Here we describe PPα-Tyr, a designed peptide comprising an α-helix buttressed by a polyproline II helix. PPα-Tyr is water soluble and monomeric, and it unfolds cooperatively with a midpoint unfolding temperature (T M ) of 39 °C. NMR structures of PPα-Tyr reveal proline residues docked between tyrosine side chains, as designed. The stability of PPα is sensitive to modifications in the aromatic residues: replacing tyrosine with phenylalanine, i.e., changing three solvent-exposed hydroxyl groups to protons, reduces the T M to 20 °C. We attribute this result to the loss of CH-π interactions between the aromatic and proline rings, which we probe by substituting the aromatic residues with nonproteinogenic side chains. In analyses of natural protein structures, we find a preference for proline-tyrosine interactions over other proline-containing pairs, and observe abundant CH-π interactions in biologically important complexes between proline-rich ligands and SH3 and similar domains.


  • Organizational Affiliation

    School of Chemistry, University of Bristol, Bristol, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PPaOMe36Streptococcus mutansMutation(s): 0 
UniProt
Find proteins for P23504 (Streptococcus mutans serotype c (strain ATCC 700610 / UA159))
Explore P23504 
Go to UniProtKB:  P23504
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23504
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
0A1
Query on 0A1
A
L-PEPTIDE LINKINGC10 H13 N O3TYR
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Submitted: 20 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
ERASynBioUnited KingdomBB/M005615/1

Revision History  (Full details and data files)

  • Version 1.0: 2017-05-17
    Type: Initial release
  • Version 1.1: 2017-05-31
    Changes: Database references
  • Version 1.2: 2017-06-28
    Changes: Database references
  • Version 1.3: 2019-05-08
    Changes: Data collection
  • Version 1.4: 2019-10-30
    Changes: Data collection, Database references
  • Version 2.0: 2023-11-15
    Changes: Atomic model, Data collection, Database references, Derived calculations