NLM IRP Seminar Schedule
UPCOMING SEMINARS
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April 25, 2024 Ermin Hodzic
Condition-Aware Cell Type Deconvolution of Bulk Tissues -
April 30, 2024 Wenya Rowe
The conformal central charge of the spin-1/2 XX model derived from long-chain asymptotics -
May 2, 2024 OPEN
TBD -
May 7, 2024 OPEN
TBD -
May 9, 2024 Pascal Mutz
TBD
RECENT SEMINARS
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April 25, 2024 Ermin Hodzic
Condition-Aware Cell Type Deconvolution of Bulk Tissues -
April 23, 2024 OPEN
TBD -
April 16, 2024 Jaya Srivastava
Regulatory plasticity of the human genome -
April 11, 2024 Sergey Shmakov
Comprehensive survey of the TnpB RNA-guided nucleases -
April 2, 2024 Yifan Yang
Fairness and Bias in Biomedical AI
Scheduled Seminars on April 27, 2023
Contact NLM_IRP_Seminar_Scheduling@mail.nih.gov with questions about this seminar.
Abstract:
Although homologous protein sequences are expected to adopt similar structures, some amino acid substitutions can interconvert α-helices and β-sheets. Such fold switching may have occurred over evolutionary history, but supporting evidence has been limited by the: (1) abundance and diversity of sequenced genes, (2) quantity of experimentally determined protein structures, and (3) assumptions underlying the statistical methods used to infer homology. Here, we overcame these barriers by applying multiple statistical methods to a family of ~600,000 bacterial response regulator proteins. We found that their homologous DNA-binding subunits assume divergent structures: helix-turn-helix versus α-helix+β-sheet (winged helix). Phylogenetic analyses, ancestral sequence reconstruction, and AlphaFold2 models indicated that amino acid substitutions facilitated a switch from helix-turn-helix into winged helix. This structural transformation likely expanded DNA-binding specificity. Our approach uncovers an evolutionary pathway between two protein folds and provides methodology to identify secondary structure switching in other protein families.