Fine Sampling of Sequence Space for Membrane Protein Structural Biology
[Display omitted] •Membrane protein structure determination is challenging.•Membrane protein structural biology benefits from structural genomics approaches.•Good expression and detergent-stability correlate with position in sequence space.•Coarse followed by fine sampling of sequence space can incr...
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Published in | Journal of molecular biology Vol. 433; no. 15; p. 167055 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Ltd
23.07.2021
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Subjects | |
Online Access | Get full text |
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Summary: | [Display omitted]
•Membrane protein structure determination is challenging.•Membrane protein structural biology benefits from structural genomics approaches.•Good expression and detergent-stability correlate with position in sequence space.•Coarse followed by fine sampling of sequence space can increase success.
We describe an enhancement of traditional genomics-based approaches to improve the success of structure determination of membrane proteins. Following a broad screen of sequence space to identify initial expression-positive targets, we employ a second step to select orthologs with closely related sequences to these hits. We demonstrate that a greater percentage of these latter targets express well and are stable in detergent, increasing the likelihood of identifying candidates that will ultimately yield structural information. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Michael Loukeris: Data curation, Formal analysis, Investigation, Visualization, Writing – original draft. Zahra Assur Sanghai: Conceptualization, Data curation, Formal analysis, Investigation, Visualization. Jeremie Vendome: Conceptualization, Formal analysis, Investigation, Visualization. Wayne A. Hendrickson: Formal analysis, Funding acquisition. Brian Kloss: Formal analysis, Project administration, Supervision, Visualization, Writing – original draft, Writing – review and editing. Filippo Mancia: Conceptualization, Formal analysis, Funding acquisition, Project administration, Supervision, Writing – original draft, Writing – review and editing. CRediT author statement |
ISSN: | 0022-2836 1089-8638 |
DOI: | 10.1016/j.jmb.2021.167055 |