Quantitative Determination of the Conformational Properties of Partially Folded and Intrinsically Disordered Proteins Using NMR Dipolar Couplings

Malene Ringkjobing Jensen, Phineus R. L. Markwick, Sebastian Meier, Christian Griesinger, Markus Zweckstetter, Stephan Grzesiek, Pau Bernado, Martin Blackledge

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Intrinsically disordered proteins (IDPs) inhabit a conformational landscape that is too complex to be described by classical structural biology, posing an entirely new set of questions concerning the molecular understanding of functional biology. The characterization of the conformational properties of IDPs, and the elucidation of the role they play in molecular function, is therefore one of the major challenges remaining for modern structural biology. NMR is the technique of choice for studying this class of proteins, providing information about structure, flexibility, and interactions at atomic resolution even in completely disordered states. In particular, residual dipolar couplings (RDCs) have been shown to be uniquely sensitive and powerful tools for characterizing local and long-range structural behavior in disordered proteins. In this review we describe recent applications of RDCs to quantitatively describe the level of local structure and transient long-range order in IDPs involved in viral replication, neurodegenerative disease, and cancer. © 2009 Elsevier Ltd. All rights reserved.
Original languageEnglish
JournalStructure
Volume17
Issue number9
Pages (from-to)1169-1185
Number of pages17
ISSN0969-2126
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • Humans
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation
  • Protein Folding
  • Tumor Suppressor Protein p53
  • amino acid derivative
  • protein derivative
  • protein p53
  • tau protein
  • alpha helix
  • Alzheimer disease
  • amino acid sequence
  • amino terminal sequence
  • analytic method
  • carboxy terminal sequence
  • crystal structure
  • degenerative disease
  • disease course
  • gene mutation
  • human
  • malignant neoplastic disease
  • molecular biology
  • molecular dynamics
  • molecular probe
  • nonhuman
  • nuclear magnetic resonance spectroscopy
  • priority journal
  • protein binding
  • protein conformation
  • protein defect
  • protein determination
  • protein folding
  • protein function
  • protein interaction
  • protein localization
  • protein motif
  • protein structure
  • protein variant
  • proton nuclear magnetic resonance
  • quantitative analysis
  • reproducibility
  • review
  • structure analysis
  • PROTEINS
  • BIOCHEMISTRY
  • BIOPHYSICS
  • CELL
  • NATIVELY UNFOLDED PROTEINS
  • 8 M UREA
  • LONG-RANGE INTERACTIONS
  • CHEMICAL-SHIFT DATA
  • X-RAY-SCATTERING
  • ALPHA-SYNUCLEIN
  • SECONDARY STRUCTURE
  • DENATURED STATE
  • UNSTRUCTURED PROTEINS
  • MOLECULAR RECOGNITION
  • conformational property
  • partial folding
  • residual dipolar coupling
  • structural biology
  • viral replication
  • cancer Neoplasms (MeSH) neoplastic disease
  • neurodegenerative disease Neurodegenerative Diseases (MeSH) nervous system disease
  • intrinsically disordered proteins
  • 10060, Biochemistry studies - General
  • 20506, Nervous system - Pathology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • nuclear magnetic resonance NMR laboratory techniques, spectrum analysis techniques
  • Biochemistry and Molecular Biophysics
  • Methods and Techniques

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