Higher-Order Structure and Protein Aggregate Characterization of Protein Therapeutics: Perspectives from Good Manufacturing Practices and Regulatory Guidance

Author(s):  
Evi B. Struble ◽  
John F. Cipollo ◽  
Chava Kimchi-Sarfaty ◽  
Zuben E. Sauna ◽  
Jack A. Ragheb ◽  
...  
2020 ◽  
Vol 199 ◽  
pp. 103973 ◽  
Author(s):  
David A. Sheen ◽  
Vincent K. Shen ◽  
Robert G. Brinson ◽  
Luke W. Arbogast ◽  
John P. Marino ◽  
...  

2013 ◽  
Vol 14 (2) ◽  
pp. 199-208 ◽  
Author(s):  
Radhika P. Nagarkar ◽  
Brian M. Murphy ◽  
Xiaotong Yu ◽  
Mark Cornell Manning ◽  
Wasfi A. Al-Azzam

Biopolymers ◽  
2009 ◽  
Vol 91 (4) ◽  
pp. 256-264 ◽  
Author(s):  
Jingjie Mo ◽  
Gabrielle C. Todd ◽  
Kristina Håkansson

2021 ◽  
Author(s):  
Keda Zhou ◽  
Magdalena Gebala ◽  
Dustin C Woods ◽  
Kousik Sundararajan ◽  
Garrett Edwards ◽  
...  

The histone variant CENP-A is the epigenetic determinant for the centromere, where it is interspersed with canonical H3 to form a specialized chromatin structure that nucleates the kinetochore. The arrangement of nucleosomes at the centromere into higher order structure is unknown. Here we demonstrate that the CENP-A interacting protein CENP-N promotes the stacking of CENP-A containing mono-nucleosomes and nucleosomal arrays through a previously undefined interaction between the α6 helix of CENP-N with the DNA of a neighboring nucleosome. We describe the cryoEM structures and biophysical characterization of such CENP-N mediated nucleosome stacks and nucleosomal arrays and demonstrate that this interaction is responsible for the formation of densely packed chromatin at the centromere in the cell. Our results provide first evidence that CENP-A, together with CENP-N, promotes specific chromatin higher order structure at the centromere.


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