David's theory of evolution: God's error corrections III (Evolution)

by David Turell @, Tuesday, October 20, 2020, 19:50 (361 days ago) @ David Turell

Another way of handling misfolded molecules:


"AAT is a protein produced by the liver and transported through the blood to the lungs, where it protects them from damage caused by other enzymes that breakdown proteins in the lung. The Z mutation produces a defective AAT protein that cannot fold into an appropriate 3-D conformation. Inappropriately folded AAT-Z proteins cannot exit the liver, so they do not travel to the lungs to protect them from destruction. This can lead to lung damage contributing to emphysema and other lung conditions.

"'As I studied the disease, I noticed that AAT-Z, which should be released from the liver, was actually accumulating," Sifers said. "This suggested that the naturally disposing mechanism of the cell might not be working."

"Sifers and others dug deeper into how cells dispose of misfolded proteins. They discovered that cells shuttle defective proteins from their place of synthesis, the endoplasmic reticulum (ER), to the cytosol, where they are degraded in a cellular structure called a proteasome. Key to this process is to tag the proteins for destruction.

"'We showed that removing certain sugars from proteins would flag them for degradation," Sifers said. "Specifically, we found that the human enzyme mannosidase Man1b1 acted like a quality-control factor that mediated the removal of the sugar mannose from misfolded AAT-Z proteins, promoting their degradation."


"They showed that certain genetic modification, a single nucleotide polymorphism, that leads to changes in the expression of the Man1b1 gene results in lower levels of Man1b1protein in the endoplasmic reticulum of liver cells.

"Sifers and colleagues proposed that lower levels of Man1b1 impair the liver's capacity to deal with the accumulation of misfolded AAT-Z. This likely accelerates reaching the tolerable threshold for protein accumulation,


"As Sifers and colleagues continued studying Man1b1, they unexpectedly came across a role for this protein that had not been described before.

"'We found that, in addition to tagging misfolded proteins for degradation by enzymatically removing mannose groups, Man1b1 also promotes protein degradation by another mechanism that is independent from the first," Sifers said.

"Sifers and his co-authors, Dr. Ashlee H. Sun, now at Polypus-transfection Biotechnology, and Dr. John R. Collette, postdocs in his lab, reported in the Proceedings of the National Academy of Sciences, that the conventional enzymatic removal system resides in one side of Man1b1, the C-terminal domain. In contrast, the new unconventional system is controlled by the other side of Man1b1, the N-terminal domain. Further studies will elucidate whether and how both systems operate in synergy."

Comment: All of this comes from studying rare genetic deficiency diseases and finds obscure God's editing mechanisms. showing He recognized/anticipated genetic errors as well as metabolic errors.

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