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CSB Research: Tilting retromer to improve the model

Posted by on Friday, January 13, 2023 in News.

Top, L to R: Amy Kendall, Mintu Chandra Bottom, L to R: Will Wan, Lauren Jackson

Does your protein of interest show favored orientations in cryo-EM? Or perhaps one specific region is poorly resolved relative to another? If so, consider looking into this recent publication from Amy Kendall, Mintu Chandra, Will Wan and Lauren Jackson.

Their findings, published in the Journal of Biological Chemistry, report an improved model of the retromer trafficking protein by collecting data with a ±15° tilt. When combined with their previous data, these tilted data sets

Figure comparing new (A, C, E) and old (B, D, F) retromer reconstructions. A/B show reconstructions with fitted models, C/D show local resolution maps, and E/F show angular distributions. Adapted from Kendall, Chandra, et al.

increased resolution and revealed more complete interaction interfaces.

Biologically, trafficking proteins play a vital role in cells to help diverse cargo fold correctly and travel to their proper compartments. Dysregulation of these processes contributes to neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.

Ultimately, these improved retromer models could lead to testable hypotheses relating to retromer function and its role in disease. Read the article here! ~S.D.W.

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