ArticleProceedings of the National Academy of Sciences of the United States of America2019
Interaction specificity of clustered protocadherins inferred from sequence covariation and structural analysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Surface delivery quantification reveals distinct trafficking efficiencies among clustered protocadherin isoforms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cadherin dynamics and cortical tension in remodeling cell-cell adhesion during EMT.Biophysical journal · 2025Article
- DCHS1 Modulates Forebrain Proportions in Modern Humans via a Glycosylation Change.bioRxiv : the preprint server for biology · 2025Article
- Characterization of transcriptional profiles associated with stress-induced neuronal activation in Arc-GFP mice.Molecular psychiatry · 2024Article
- Clustered protocadherinProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Advances in modeling cellular mechanical perceptions and responses via the membrane-cytoskeleton-nucleus machinery.Mechanobiology in medicine · 2024Review
- Marginal specificity in protein interactions constrains evolution of a paralogous family.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structure of the planar cell polarity cadherins Fat4 and Dachsous1.Nature communications · 2023Article
- General strategies for using amino acid sequence data to guide biochemical investigation of protein function.Biochemical Society transactions · 2022Review
- Elastic versus brittle mechanical responses predicted for dimeric cadherin complexes.Biophysical journal · 2022Article
- Modeling the Dynamics of Protein-Protein Interfaces, How and Why?Molecules (Basel, Switzerland) · 2022Review
- How clustered protocadherin binding specificity is tuned for neuronal self-/nonself-recognition.eLife · 2022Article
- The Conserved Serine Transporter SdaC Moonlights To Enable Self Recognition.Journal of bacteriology · 2022Article
- Heterophilic and homophilic cadherin interactions in intestinal intermicrovillar links are species dependent.PLoS biology · 2021Article
- Data-driven computational protein design.Current opinion in structural biology · 2021Review
- Crystal structure of the nonclassical cadherin-17 N-terminus and implications for its adhesive binding mechanism.Acta crystallographica. Section F, Structural biology communications · 2021Article
- Wiring the Brain by Clustered Protocadherin Neural Codes.Neuroscience bulletin · 2021Review
- Predicting the Specificity- Determining Positions of Receptor Tyrosine Kinase Axl.Frontiers in molecular biosciences · 2021Article
- Chelicerata sDscam isoforms combine homophilic specificities to define unique cell recognition.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Clustered Protocadherins Emerge as Novel Susceptibility Loci for Mental Disorders.Frontiers in neuroscience · 2020Review
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7 authors.
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Abstract
Clustered protocadherins, a large family of paralogous proteins that play important roles in neuronal development, provide an important case study of interaction specificity in a large eukaryotic protein family. A mammalian genome has more than 50 clustered protocadherin isoforms, which have remarkable homophilic specificity for interactions between cellular surfaces. A large antiparallel dimer interface formed by the first 4 extracellular cadherin (EC) domains controls this interaction. To understand how specificity is achieved between the numerous paralogs, we used a combination of structural and computational approaches. Molecular dynamics simulations revealed that individual EC interactions are weak and undergo binding and unbinding events, but together they form a stable complex through polyvalency. Strongly evolutionarily coupled residue pairs interacted more frequently in our simulations, suggesting that sequence coevolution can inform the frequency of interaction and biochemical nature of a residue interaction. With these simulations and sequence coevolution, we generated a statistical model of interaction energy for the clustered protocadherin family that measures the contributions of all amino acid pairs at the interface. Our interaction energy model assesses specificity for all possible pairs of isoforms, recapitulating known pairings and predicting the effects of experimental changes in isoform specificity that are consistent with literature results. Our results show that sequence coevolution can be used to understand specificity determinants in a protein family and prioritize interface amino acid substitutions to reprogram specific protein-protein interactions.
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