Probing the structure of folding intermediates

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Abstract

The description of protein folding mechanisms in terms of the structures of well defined, partially folded intermediates is a major objective in structural biology. Despite the fleeting existence of intermediates and the fact that their structures are unlikely to be uniquely defined, significant advances in our understanding of protein folding pathways have been made in the last year based on a variety of physical methods.

References (54)

  • K. Kuwajima

    The Molten Globule as a Clue for Understanding the Folding and Cooperativity of Globular Protein Structures

    Proteins — Struct Funct Genet

    (1989)
  • G.A. Elöve et al.

    Early Steps in Cytochrome c Folding Probed by Time-Resolved Circular Dichroism and Fluorescence Spectroscopy

    Biochemistry

    (1992)
  • S.E. Radford et al.

    The Folding of Hen Lysozyme Involves Partially Structured Intermediates and Multiple Pathways

    Nature

    (1992)
  • S. Khorazanizadeh et al.

    Folding and Stability of a Tryptophan Containing Mutant of Ubiquitin

    Biochemistry

    (1993)
  • T. Kiefhaber et al.

    Structure of a Rapidly Formed Intermediate in Ribonuclease TI Folding

    Protein Science

    (1992)
  • C.M. Dobson

    Unfolded Proteins, Compact States and Molten Globules

    Curr Opin Struct Biol

    (1992)
  • J. Sancho et al.

    An N-Terminal Fragment of Barnase has Residual Helical Structure Similar to that in a Refolding Intermediate

    J Mol Biol

    (1992)
  • L.C. Wu et al.

    A Non-Covalent Peptide Complex as a Model for an Early Folding Intermediate of Cytochrome c

    Biochemistry

    (1993)
  • D. Shortle

    Denatured States of Proteins and their Role in Folding and Stability

    Curr Opin Struct Biol

    (1993)
  • D. Neri et al.

    NMR Determination of Residual Structure in a Urca-Denatured Protein, the 434 Repressor

    Science

    (1992)
  • P.A. Evans et al.

    Hydrophobic Clustering in Non-Native States of a Protein: Interpretation of Chemical Shifts in NMR Spectra of Denatured States of Lysozyme

    Proteins

    (1991)
  • G. Chelvanayagam et al.

    Prediction of Protein Folding Pathways

    J Mol Biol

    (1992)
  • S. Vajda

    Conformational Filtering in Polypeptides and Proteins

    J Mol Biol

    (1993)
  • A. Godzik et al.

    Simulations of the Folding Pathway of Triose Phosphate Isomerase-Type α/β Barrel Proteins

  • C.J. Camacho et al.

    Kinetics and Thermodynamics of Folding in Model Proteins

    Proc Natl Acad Sci USA

    (1993)
  • V. Daggett et al.

    Protein Unfolding Pathways Explored through Molecular Dynamics Simulations

    J Mol Biol

    (1993)
  • J. Clarke et al.

    Local Breathing and Global Unfolding in Hydrogen Exchange of Barnasc and its Relationship to Protein Folding pathways

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