+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Destruction of long-range interactions by a single mutation in lysozyme



Destruction of long-range interactions by a single mutation in lysozyme



Proceedings of the National Academy of Sciences of the United States of America 104(14): 5824-5829



We propose a mechanism, based on a > or =10-micros molecular dynamics simulation, for the surprising misfolding of hen egg-white lysozyme caused by a single mutation (W62G). Our simulations of the wild-type and mutant lysozymes in 8 M urea solution at biological temperature (with both pH 2 and 7) reveal that the mutant structure is much less stable than that of the wild type, with the mutant showing larger fluctuations and less native-like contacts. Analysis of local contacts reveals that the Trp-62 residue is the key to a cooperative long-range interaction within the wild type, where it acts like a bridge between two neighboring basic residues. Thus, a native-like cluster or nucleation site can form near these residues in the wild type but not in the mutant. The time evolution of the secondary structure also exhibits a quicker loss of the beta-sheets in the mutant than in the wild type, whereas some of the alpha-helices persist during the entire simulation in both the wild type and the mutant in 8 M urea (even though the tertiary structures are basically all gone). These findings, while supporting the general conclusions of a recent experimental study by Dobson and coworkers [Klein-Seetharam J, Oikama M, Grimshaw SB, Wirmer J, Duchardt E, Ueda T, Imoto T, Smith LJ, Dobson CM, Schwalbe H (2002) Science 295:1719-1722], provide a detailed but different molecular picture of the misfolding mechanism.

(PDF emailed within 0-6 h: $19.90)

Accession: 013680800

Download citation: RISBibTeXText

PMID: 17389393

DOI: 10.1073/pnas.0701249104


Related references

Modulation of compactness and long-range interactions of unfolded lysozyme by single point mutations. Angewandte Chemie 43(43): 5780-5785, 2004

Role of medium- and long-range interactions to the stability of the mutants of T4 lysozyme. Preparative Biochemistry & Biotechnology 31(3): 217-227, 2001

Local versus long range interactions among antibodies recognizing a complex antigenic region on lysozyme. FASEB Journal 4(7): A2086, 1990

Single-molecule studies of repressor-DNA interactions show long-range interactions. Proceedings of the National Academy of Sciences of the United States of America 102(28): 9796-9801, 2005

Time resolved emissions in the picosecond range of single tryptophan recombinant myoglobins reveal the presence of long range heme protein interactions. Biophysical Chemistry 74(3): 187-196, Sept 14, 1998

Cumulative site-directed charge-change replacements in bacteriophage T4 lysozyme suggest that long-range electrostatic interactions contribute little to protein stability. Journal of Molecular Biology 221(3): 873-887, 1991

Introduction of short-range restrictions in a protein-folding algorithm involving a long-range geometrical restriction and short-, medium-, and long-range interactions. Proceedings of the National Academy of Sciences of the United States of America 78(11): 6584-6587, 1981

Short-range interactions and size of ligands bound to DNA strongly influence adsorptive phase transition caused by long-range interactions. Journal of Biomolecular Structure & Dynamics 19(6): 1093-1100, 2002

Single-file diffusion of particles with long-range interactions: damping and finite-size effects. Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics 84(1 Pt 1): 011101-011101, 2012

Time resolved emissions of single tryptophan myoglobins reveal long range heme protein interactions. FASEB Journal 12(8): A1425, April 24, 1998

Higher order spectrum analysis of long range lateral interactions Cat single units and human VEPS. Investigative Ophthalmology & Visual Science 37(3): S483, 1996

Nature of long-range order in stripe-forming systems with long-range repulsive interactions. Physical Review Letters 114(11): 116101-116101, 2015

Model of protein folding inclusion of short range medium range and long range interactions. Proceedings of the National Academy of Sciences of the United States of America 72(10): 3802-3806, 1975

Long-range tertiary interactions in single hammerhead ribozymes bias motional sampling toward catalytically active conformations. Rna 16(12): 2414-2426, 2010

Lysozyme-lysozyme and lysozyme-salt interactions in the aqueous saline solution: a new square-well potential. Biomacromolecules 4(6): 1713-1718, 2003