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Cited by 216Protein Structure and DynamicsForce Microscopy Techniques and ApplicationsHealthcare Operations and Scheduling Optimization

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Non-attendance at general practices and outpatient clinics: Local systems are needed to address local problems

Open access
Sharp, Deborah J, Hamilton, William·2001·BMJ
DOI 10.1136/bmj.323.7321.1081PMC PMC1121587
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Abstract

Abstract Tandem-repeat proteins comprise small secondary structure motifs that stack to form one-dimensional arrays with distinctive mechanical properties that are proposed to direct their cellular functions. Here, we use single-molecule optical tweezers to study the folding of consensus-designed tetratricopeptide repeats (CTPRs) — superhelical arrays of short helix-turn-helix motifs. We find that CTPRs display a spring-like mechanical response in which individual repeats undergo rapid equilibrium fluctuations between folded and unfolded conformations. We rationalise the force response using Ising models and dissect the folding pathway of CTPRs under mechanical load, revealing how the repeat arrays form from the centre towards both termini simultaneously. Strikingly, we also directly observe the protein’s superhelical tertiary structure in the force signal. Using protein engineering, crystallography and single-molecule experiments, we show how the superhelical geometry can be altered by carefully placed amino-acid substitutions and examine how these sequence changes affect intrinsic repeat stability and inter-repeat coupling. Our findings provide the means to dissect and modulate repeat-protein stability and dynamics, which will be essential for researchers to understand the function of natural repeat proteins and to exploit artificial repeats proteins in nanotechnology and biomedical applications. Significance statement Repetition of biological building blocks is crucial to modulating and diversifying structure and function of biomolecules across all organisms. In tandem-repeat proteins, the linear arrangement of small structural motifs leads to the formation of striking supramolecular shapes. Using a combination of single-molecule biophysical techniques and modelling approaches, we dissect the spring-like nature of a designed repeat protein and demonstrate how its shape and mechanics can be manipulated by design. These novel insights into the biomechanical and biochemical characteristics of this protein class give us a methodological basis from which to understand the biological functions of repeat proteins and to exploit them in nanotechnology and biomedicine.

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Research works printed but not linked: 3

  1. Beauchant, 1997, Socio-economic and demographic factors in patient non-attendance., Br J Healthcare Manage, 3, 523
  2. 2000, Impact, 2, 5
  3. Read, 1997, Dial a clinic—a new approach to reducing the number of defaulters., Br J Healthcare Manage, 3, 307

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Metadata

Authors
Sharp, D. J., & Hamilton, W.
Affiliations
University of Bristol (GB)
Corresponding author
Hamilton, William
ORCID
Hamilton, William
Venue
BMJ
Publisher
BMJ
Published
2001-11-10
Volume
323
Issue
7321
Pages
1081-1082
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
DOI
10.1136/bmj.323.7321.1081
PMC
PMC1121587
OpenAlex
W2093063118
Cited by
216
References
10
Citations by year
2026: 2 · 2025: 6 · 2024: 10 · 2023: 5 · 2022: 13 · 2021: 11 · 2020: 12 · 2019: 8 · 2018: 15 · 2017: 12 · 2016: 8 · 2015: 11 · 2014: 17 · 2013: 7 · 2012: 17
Type
journal article
Language
en
Open access
Licence
www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
Locations
  • BMJ (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
  • Social Sciences › Decision Sciences › Management Science and Operations Research › Healthcare Operations and Scheduling Optimization
Keywords
non-attendance, general practice, outpatient clinics, health care access, patient attendance
MeSH terms
Appointments and Schedules, Family Practice, United Kingdom, Humans, Outpatient Clinics, Hospital, Patient Acceptance of Health Care, Patient Dropouts

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