What makes a protein a protein? Hydrophobic core designs that specify stability and structural properties.


Abstract

Here we describe how the systematic redesign of a protein's hydrophobic core alters its structure and stability. We have repacked the hydrophobic core of the four-helix-bundle protein, Rop, with altered packing patterns and various side chain shapes and sizes. Several designs reproduce the structure and native-like properties of the wild-type, while increasing the thermal stability. Other designs, either with similar sizes but different shapes, or with decreased sizes of the packing residues, destabilize the protein. Finally, overpacking the core with the larger side chains causes a loss of native-like structure. These results allow us to further define the roles of tight residue packing and the burial of hydrophobic surface area in the construction of native-like proteins. Study holds ProTherm entries: 8636, 8637, 8638 Extra Details: hydrophobic core; molecular packing; molten globule; protein design

Submission Details

ID: 2Vdd5Q2T4

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:36 p.m.

Version: 1

Publication Details
Munson M;Balasubramanian S;Fleming KG;Nagi AD;O'Brien R;Sturtevant JM;Regan L,Protein Sci. (1996) What makes a protein a protein? Hydrophobic core designs that specify stability and structural properties. PMID:8844848
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1RPR 1994-01-31 THE STRUCTURE OF COLE1 ROP IN SOLUTION
1NKD 1999-03-23 1.09 ATOMIC RESOLUTION (1.07 ANGSTROMS) STRUCTURE OF THE ROP MUTANT <2AA>
4DO2 2013-02-13 1.4 Crystal Structure of the Rop protein mutant D30P/A31G at resolution 1.4 resolution.
1RPO 1995-02-14 1.4 RESTORED HEPTAD PATTERN CONTINUITY DOES NOT ALTER THE FOLDING OF A 4-ALPHA-HELICAL BUNDLE
2IJK 2007-10-16 1.55 Structure of a Rom protein dimer at 1.55 angstrom resolution
1ROP 1992-07-15 1.7 STRUCTURE OF THE COL*E1 ROP PROTEIN AT 1.7 ANGSTROMS RESOLUTION
1B6Q 1999-07-09 1.8 ALANINE 31 PROLINE MUTANT OF ROP PROTEIN
2IJH 2007-10-16 1.8 Crystal structure analysis of ColE1 ROM mutant F14W
1GTO 1997-01-27 1.82 HIGH RESOLUTION STRUCTURE OF A HYPERSTABLE HELICAL BUNDLE PROTEIN MUTANT
1F4N 2001-01-10 1.9 C2 CRYSTAL STRUCTURE OF ALA2ILE2-6, A VERSION OF ROP WITH A REPACKED HYDROPHOBIC CORE AND A NEW FOLD.
2IJJ 2007-10-16 1.9 Crystal structure analysis of ColE1 ROM mutant F14Y
1GMG 2002-09-12 1.9 ALANINE 31 PROLINE MUTANT OF ROP PROTEIN, MONOCLINIC FORM
3K79 2010-02-02 1.96 C38A, C52V Cysteine-Free Variant of Rop (Rom)
1QX8 2004-09-28 2.02 Crystal structure of a five-residue deletion mutant of the Rop protein
1F4M 2001-01-10 2.25 P3(2) CRYSTAL STRUCTURE OF ALA2ILE2-6, A VERSION OF ROP WITH A REPACKED HYDROPHOBIC CORE AND A NEW FOLD.
2IJI 2007-10-16 2.3 Structure of F14H mutant of ColE1 Rom protein
2GHY 2006-05-30 2.5 Novel Crystal Form of the ColE1 Rom Protein
1YO7 2005-02-15 2.8 Re-engineering topology of the homodimeric ROP protein into a single-chain 4-helix bundle

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Regulatory protein rop P03051 ROP_ECOLX