scission_analysis

scission_analysis analyzes membrane scission events during clathrin-mediated endocytosis (CME), focusing on dynamin GTPase interactions and multivalent binding between the proline/arginine-rich domain (dynPRD) and Src-homology 3 (SH3) domains to assess effects on vesicle scission.

Key Features:

• Focus on dynamin-interacting partners: Emphasizes dynPRD binding to SH3 domains of proteins such as amphiphysins and the role of these interactions in recruiting dynamin during CME.
• Multivalent interaction analysis: Incorporates data on simultaneous binding of multiple SH3 domains to the three adjacent motifs in dynPRD and compares divalent versus monovalent dynPRD-derived peptide binding to amphSH3 multimers.
• Functional impact assessment: Models the functional consequences of mutations in dynPRD motifs, including partial rescue by single-motif mutations and loss of rescue with double-motif mutations in dynamin triple knock-out cells.
• Experimental simulation capabilities: Simulates experimental conditions such as intracellular delivery of divalent and monovalent peptides (e.g., via patch-clamp pipettes) to evaluate their differential blocking effects on CME.

Scientific Applications:

• Molecular mechanism studies: Investigating structural and functional dynamics of dynamin and its SH3-containing partners during vesicle scission.
• Intervention analysis: Exploring modulation of CME by multivalent interactions and testing peptide-based perturbations.
• Genotype–phenotype analysis: Analyzing effects of genetic mutations in dynPRD–SH3 binding motifs on endocytic pathways, including in dynamin triple knock-out cells.

Methodology:

Incorporates data on multivalent dynPRD–SH3 binding, models effects of single and double motif mutations in dynamin triple knock-out cells, and simulates peptide intervention experiments comparing divalent and monovalent dynPRD-derived peptides delivered via patch-clamp pipettes.