They all rock: A systematic comparison of conformational movements in LeuT-fold transporters
Open accessPublished version of a preprint
Abstract
Many membrane transporters share the LeuT fold-two five-helix repeats inverted across the membrane plane. Despite hundreds of structures, whether distinct conformational mechanisms are supported by the LeuT fold has not been systematically determined. After annotating published LeuT-fold structures, we analyzed distance difference matrices (DDMs) for nine proteins with multiple available conformations. We identified rigid bodies and relative movements of transmembrane helices (TMs) during distinct steps of the transport cycle. In all transporters, the bundle (first two TMs of each repeat) rotates relative to the hash (third and fourth TMs). Motions of the arms (fifth TM) to close or open the intracellular and outer vestibules are common, as is a TM1a swing, with notable variations in the opening-closing motions of the outer vestibule. Our analyses suggest that LeuT-fold transporters layer distinct motions on a common bundle-hash rock and demonstrate that systematic analyses can provide new insights into large structural datasets.
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Cites
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A large‐scale evolutionary and structural analysis of <scp>CLC</scp> channels and transporters
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“These DDMs, report positive and negative distance deviations corresponding to regions of expansion or compression, and have been used previously to analyze defined conformational changes (Licht et al., 2024).”
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- Authors
- Licht, J. A., Berry, S. P., Gutierrez, M. A., & Gaudet, R.
- Affiliations
- Harvard University (US)
- Corresponding author
- Gaudet, Rachelle
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2024-09
- Volume
- 32
- Issue
- 9
- Pages
- 1528-1543.e3
- ISSN
- 0969-2126 (ISSN-L)
- PMC
- PMC11380583
- OpenAlex
- W4400732226
- Cited by
- 19
- References
- 5
- Citations by year
- 2026: 8 · 2025: 11
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Structure (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- Funders
- National Science Foundation (1764269)
- National Institutes of Health
- Key Laboratory of Low-grade Energy Utilization Technology and System, Chongqing University
- National Institute of General Medical Sciences (T32GM008313, R01GM120996)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- membrane transporters, transport cycle, rigid body motion
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