The structure of a calsequestrin filament reveals mechanisms of familial arrhythmia


In a clinical collaboration with Melvin Scheinman from the UCSF Comprehensive Genetic Arrythmia Program, CVRI investigators Rahul Deo and Natalia Jura, along with MD/PhD trainee Erron Titus, set out to explain how mutations in the calcium-storage protein, calsequestrin, cause lethal arrhthymias. The team solved a new X-ray crystal structure of human cardiac calsequestrin, revealing the biochemical basis of calsequestrin’s assembly into filaments. Using the new structure, the team was able to map disease-associated mutations to the filament surfaces and explain how the location of the mutation in the structure determines the severity of disease.

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