Identifying molecular features that are associated with biological function of intrinsically disordered protein regions
TLDR
Zarin et al. as mentioned in this paper showed that intrinsically disordered regions (IDRs) contain sequence-distributed molecular features that are conserved over evolution, despite little sequence similarity that can be detected in alignments, and they used these molecular features to predict specific biological functions for individual IDRs and identify the molecular features within them that are associated with these functions.Abstract:
In previous work, we showed that intrinsically disordered regions (IDRs) of proteins contain sequence-distributed molecular features that are conserved over evolution, despite little sequence similarity that can be detected in alignments (Zarin et al., 2019). Here, we aim to use these molecular features to predict specific biological functions for individual IDRs and identify the molecular features within them that are associated with these functions. We find that the predictable functions are diverse. Examining the associated molecular features, we note some that are consistent with previous reports and identify others that were previously unknown. We experimentally confirm that elevated isoelectric point and hydrophobicity, features that are positively associated with mitochondrial localization, are necessary for mitochondrial targeting function. Remarkably, increasing isoelectric point in a synthetic IDR restores weak mitochondrial targeting. We believe feature analysis represents a new systematic approach to understand how biological functions of IDRs are specified by their protein sequences.read more
Citations
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Convolutions are competitive with transformers for protein sequence pretraining
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On the Potential of Machine Learning to Examine the Relationship Between Sequence, Structure, Dynamics and Function of Intrinsically Disordered Proteins
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In-Cell Structural Biology by NMR: The Benefits of the Atomic Scale.
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Phase Transitions of Associative Biomacromolecules.
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Hidden structure in disordered proteins is adaptive to intracellular changes
David Moses,Karina Guadalupe,Feng Yu,Eduardo Flores,Anthony Perez,Ralph L. McAnelly,Nora M. Shamoon,Estefania Cuevas-Zepeda,Andrea Merg,Erik W. Martin,Alex S. Holehouse,Shahar Sukenik +11 more
TL;DR: In this paper, the authors reveal hidden structural preferences in IDR ensembles in vitro with two orthogonal structural methods (SAXS and FRET) and demonstrate that these structural preferences persist in cells using live cell microscopy.
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