Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1111/febs.12809 http://scihub22266oqcxt.onion/10.1111/febs.12809 C4047191!4047191!24702826     free     free     free Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 217.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 284.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 284.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 284.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       FEBS+J 2014 ; 281 (11): 2525-42 Nephropedia Template TP {{tp|p=24702826|t=2014. Amyloidogenic Mutations in Human Apolipoprotein A-I are not Necessarily Destabilizing: A Common Mechanism of ApoA-I Misfolding in Familial Amyloidosis and Atherosclerosis |pdf=|usr=}}{{24702826}} gab.com Text Amyloidogenic Mutations in Human Apolipoprotein A-I are not Necessarily Destabilizing: A Common Mechanism of ApoA-I Misfolding in Familial Amyloidosis and Atherosclerosis JO: FEBS J http://www.kidney.de/pget.php?&tw=1&pmid=24702826 #FOAvip High-density lipoproteins (HDLs) and their major protein, apoA-I, remove excess cellular cholesterol and protect against atherosclerosis. However, in acquired amyloidosis, non-variant full-length apoA-I deposits as fibrils in atherosclerotic plaques; in familial amyloidosis, N-terminal fragments of variant apoA-I deposit in vital organs damaging them. Recently, we used the crystal structure of ?(185-243)apoA-I to propose that amyloidogenic mutations destabilize apoA-I and increase solvent exposure of the extended strand 44-55 that initiates ?-aggregation. Here we test this hypothesis by exploring naturally occurring human amyloidogenic mutations, W50R and G26R, within or close to this strand. The mutations caused small changes in the protein?s ?-helical content, stability, proteolytic pattern, and protein-lipid interactions. These changes alone were unlikely to account for amyloidosis, suggesting the importance of other factors. Sequence analysis predicted several amyloid-prone segments that can initiate apoA-I misfolding. Aggregation studies using N-terminal fragments experimentally verified this prediction. Three predicted N-terminal amyloid-prone segments, mapped on the crystal structure, formed an ?-helical cluster. Structural analysis indicates that amyloidogenic mutations or Met86 oxidation perturb native packing in this cluster. Together, the results suggest that structural perturbations in the amyloid-prone segments trigger ?-helix-to-?-sheet conversion in the N-terminal ~75 residues forming the amyloid core. Polypeptide outside this core can be proteolysed to form 9-11 kDa N-terminal fragments found in familial amyloidosis. Our results imply that apoA-I misfolding in familial and acquired amyloidosis follows a similar mechanism that does not require significant structural destabilization or proteolysis. This novel mechanism suggests potential therapeutic interventions for apoA-I amyloidosis. Twit Text FOAVip Amyloidogenic Mutations in Human Apolipoprotein A-I are not Necessarily Destabilizing: A Common Mechanism of ApoA-I Misfolding in Familial Amyloidosis and Atherosclerosis ????FEBS J http://www.kidney.de/pget.php?&tw=1&pmid=24702826 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24702826 #FOAvip English Wikipedia <ref>{{Cite pmid|24702826}}</ref> Amyloidogenic Mutations in Human Apolipoprotein A-I are not Necessarily Destabilizing: A Common Mechanism of ApoA-I Misfolding in Familial Amyloidosis and Atherosclerosis #MMPMID24702826 Das M; Mei X; Jayaraman S; Atkinson D; Gursky O FEBS J 2014[Jun]; 281 (11): 2525-42 PMID24702826show ga High-density lipoproteins (HDLs) and their major protein, apoA-I, remove excess cellular cholesterol and protect against atherosclerosis. However, in acquired amyloidosis, non-variant full-length apoA-I deposits as fibrils in atherosclerotic plaques; in familial amyloidosis, N-terminal fragments of variant apoA-I deposit in vital organs damaging them. Recently, we used the crystal structure of ?(185-243)apoA-I to propose that amyloidogenic mutations destabilize apoA-I and increase solvent exposure of the extended strand 44-55 that initiates ?-aggregation. Here we test this hypothesis by exploring naturally occurring human amyloidogenic mutations, W50R and G26R, within or close to this strand. The mutations caused small changes in the protein?s ?-helical content, stability, proteolytic pattern, and protein-lipid interactions. These changes alone were unlikely to account for amyloidosis, suggesting the importance of other factors. Sequence analysis predicted several amyloid-prone segments that can initiate apoA-I misfolding. Aggregation studies using N-terminal fragments experimentally verified this prediction. Three predicted N-terminal amyloid-prone segments, mapped on the crystal structure, formed an ?-helical cluster. Structural analysis indicates that amyloidogenic mutations or Met86 oxidation perturb native packing in this cluster. Together, the results suggest that structural perturbations in the amyloid-prone segments trigger ?-helix-to-?-sheet conversion in the N-terminal ~75 residues forming the amyloid core. Polypeptide outside this core can be proteolysed to form 9-11 kDa N-terminal fragments found in familial amyloidosis. Our results imply that apoA-I misfolding in familial and acquired amyloidosis follows a similar mechanism that does not require significant structural destabilization or proteolysis. This novel mechanism suggests potential therapeutic interventions for apoA-I amyloidosis. äAmyloidogenic Mutations in Human Apolipoprotein A-I are not Necessaril(epmc).pdf DeepDyve Pubget Overpricing