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Nanomechanics of Proteins, Both Folded and Disordered

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Single-molecule Studies of Proteins

Part of the book series: Biophysics for the Life Sciences ((BIOPHYS,volume 2))

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Abstract

Single-molecule techniques have recently provided a versatile tool for imaging and manipulating protein molecules one at a time, enabling us to address important biological questions in key areas of cell biology (e.g., cell adhesion and signaling, neurodegeneration) and protein science (e.g., protein folding, protein structure and stability, catalysis, protein evolution, conformational polymorphism, and amyloidogenesis). One of these techniques, single-molecule force spectroscopy based on atomic force microscopy, combined with theoretical/computational approaches and protein engineering, has allowed unprecedented progress in characterizing and understanding at the molecular level the mechanical properties of biomolecules, particularly those of proteins, which has recently opened the new, exciting and fast-growing research field of protein nanomechanics. The aim of this review is to describe the principles of this methodology and to discuss the main achievements in this field, with special emphasis on its emerging application to the analysis of intrinsically disordered proteins.

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Abbreviations

AFM:

Atomic force microscopy

Arc:

Arctic

Aβ:

Amyloid beta

CaM:

Calmodulin

D2 :

Disorder in disorder

DHF:

7,8-Dihydrofolate

DHFR:

Dihydrofolate reductase

DMSO:

Dimethyl sulfoxide

ELP:

Elastin-like-polypeptides

F U :

Unfolding force

GB1:

B1 immunoglobulin binding domain of streptococcal protein G

HD:

Huntington’s disease

hM:

Hyper-mechanostable

IDP:

Intrinsically disordered protein

Ig:

Immunoglobulin

L C :

Contour length

M:

Mechanostable

MBP:

Maltose binding protein

mtx:

Methotrexate

N A :

Avogadro’s number

NADPH:

Nicotinamide adenine dihydrogen phosphate

NM:

Non-mechanostable

NMR:

Nuclear magnetic resonance

p :

Persistence length

PC1:

Polycystin-1

pFS:

Plasmid for force spectroscopy

PKA:

Protein kinase A

PolyQ:

Polyglutamine

QBP1:

PolyQ binding peptide 1

RC:

Random coil

SMD:

Steered molecular dynamics

SMF:

Single-molecule fluorescence

SMFS:

Single-molecule force spectroscopy

SMT:

Single-molecule techniques

SPM:

Scanning probe microscopy

S–S:

Disulfide bond

STM:

Scanning tunneling microscope

THF:

5,6,7,8-Tetrahydrofolate

TNfn3:

Third fibronectin type III domain

TNXfn7:

Seventh FnIII domain of human tenascin-X

TS:

Transition state

WLC:

Worm-like chain

α-syn:

Alpha synuclein

ΔL C :

Contour length increase

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Acknowledgments

We thank Douglas Laurents (Instituto Química-Física Rocasolano, IQFR-CSIC), Andrés Oberhauser (University of Texas Medical Branch), Marek Cieplak (Polish Academy of Science), Javier Oroz (Centro de Investigaciones Biológicas, CIB-CSIC) and Andrés M. Vera (Instituto Cajal, IC-CSIC) for the critical reading of the manuscript. This work was funded by grants from the Ministerio de Ciencia e Innovación (MICINN-BIO2007-67116), the Consejería de Educación de la Comunidad de Madrid (S-0505/MAT/0283), and the Consejo Superior de Investigaciones Científicas (CSIC- 200620F00) to MCV. We apologize to all researchers whose pioneering work was not cited due to limitations of space.

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  1. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto Cajal, IC-CSIC, Madrid, Spain

    Rubén Hervás, Albert Galera-Prat, Àngel Gómez-Sicilia, Fernando Losada-Urzáiz, María del Carmen Fernández, Débora Fernández-Bravo, Elena Santana, Clara Barrio-García, Carolina Melero & Mariano Carrión-Vázquez

  2. Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA-Nanociencia), Madrid, Spain

    Rubén Hervás, Albert Galera-Prat, Àngel Gómez-Sicilia, Fernando Losada-Urzáiz, María del Carmen Fernández, Débora Fernández-Bravo, Elena Santana, Clara Barrio-García, Carolina Melero & Mariano Carrión-Vázquez

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  1. Rubén Hervás
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Correspondence to Mariano Carrión-Vázquez .

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  1. , Neuroscience and Cell Biology, University of Texas Medical Branch, 5.212A Research Building 17, Galveston, 77555-0620, Texas, USA

    Andres F. Oberhauser

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Hervás, R. et al. (2012). Nanomechanics of Proteins, Both Folded and Disordered. In: Oberhauser, A. (eds) Single-molecule Studies of Proteins. Biophysics for the Life Sciences, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4921-8_1

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