老泉2019-08-04 15:01:59回複悄悄話
老閻九三文章，那個示意圖根本沒談機理，隻是標出了三個區域而異。文章寫道："although we can identify a residual within the translocation pathway of UhPT, we cannot yet comment on how this pathway may operate”.
老閻九三文章 is about identifying a residue C265 and 3 domains. The famous graph he used in his blog is not about pathway mechanism, but about showing 3 domains with C265 in the core domain. As for pathway mechanism, Yan and Maloney did not know at the time and only suggested either mobile carrier (residual C265 as elevator to shuttle substrate in and out) or mobile barrier (gated pore) theory. These theories (mobile carrier or mobile barrier) are not related to outward open/inward open conformations Yan Nieng talked about in her graph (it is a simple graph used by many since 1966 to 1992, from 1992 to 2014..).
AAM theory is still just theory at this time (most viable per Mueckler in 2014 review) and more work is needed. Anyone can propose new techniques (crystal structure and x-ray or biochemical or both or other) or updated model for future research and development.
Mr. Yan's contribution is to identify 3 domains in the pathway in UhPT with his method. That gave "detailed topological" feature for the TM7 in UhPT and it provided a "compelling" physical evidence for AAM. Since then many more people provided more physical evidence for the AAM including Yan Nieng's crystal (even better evidence).
Mr. Yan's 3 domains topology for his pathway maybe right, maybe not. For other pathway, there may be more than 3 domains since there are gates inside some pathways. C265 residual discovered by Mr. Yan has not been mentioned by Mr. Maloney in his work from 1996 to 2002 since other residuals are more important for that pathway (UhPT). I wonder if anyone since 1993 repeated Mr. Yan's work about C265.
老閻九三文章 is about identifying a residue C265 and 3 domains. The famous graph he used in his blog is not about pathway mechanism, but about showing 3 domains with C265 in the core domain. As for pathway mechanism, Yan and Maloney did not know at the time and only suggested either mobile carrier (residual C265 as elevator to shuttle substrate in and out) or mobile barrier (gated pore) theory. These theories (mobile carrier or mobile barrier) are not related to outward open/inward open conformations Yan Nieng talked about in her graph (it is a simple graph used by many since 1966 to 1992, from 1992 to 2014..).
AAM theory is still just theory at this time (most viable per Mueckler in 2014 review) and more work is needed. Anyone can propose new techniques (crystal structure and x-ray or biochemical or both or other) or updated model for future research and development.
Mr. Yan's contribution is to identify 3 domains in the pathway in UhPT with his method. That gave "detailed topological" feature for the TM7 in UhPT and it provided a "compelling" physical evidence for AAM. Since then many more people provided more physical evidence for the AAM including Yan Nieng's crystal (even better evidence).
Mr. Yan's 3 domains topology for his pathway maybe right, maybe not. For other pathway, there may be more than 3 domains since there are gates inside some pathways. C265 residual discovered by Mr. Yan has not been mentioned by Mr. Maloney in his work from 1996 to 2002 since other residuals are more important for that pathway (UhPT). I wonder if anyone since 1993 repeated Mr. Yan's work about C265.