<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Doke, Abhilasha A.</style></author><author><style face="normal" font="default" size="100%">Jha, Santosh Kumar</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Deciphering the monomeric and dimeric conformational landscapes of the full-length TDP-43 and the impact of the C-terminal domain</style></title><secondary-title><style face="normal" font="default" size="100%">ACS Chemical Neuroscience</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">chain collapsibility</style></keyword><keyword><style  face="normal" font="default" size="100%">domain-wisefluctuation</style></keyword><keyword><style  face="normal" font="default" size="100%">electrostatic dominance</style></keyword><keyword><style  face="normal" font="default" size="100%">hydrogen bond switchability</style></keyword><keyword><style  face="normal" font="default" size="100%">long-range crosstalk</style></keyword><keyword><style  face="normal" font="default" size="100%">persistent beta-character</style></keyword><keyword><style  face="normal" font="default" size="100%">protagonistic C-terminal domain</style></keyword><keyword><style  face="normal" font="default" size="100%">rugged phase space</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">NOV</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">15</style></volume><pages><style face="normal" font="default" size="100%">4305-4321</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	The aberrant aggregation of TAR DNA-binding protein 43 kDa (TDP-43) in cells leads to the pathogenesis of multiple fatal neurodegenerative diseases. Decoding the proposed initial transition between its functional dimeric and aggregation-prone monomeric states can potentially design a viable therapeutic strategy, which is presently limited by the lack of structural detail of the full-length TDP-43. To achieve a complete understanding of such a delicate phase space, we employed a multiscale simulation approach that unearths numerous crucial features, broadly summarized in two categories: (1) state-independent features that involve inherent chain collapsibility, rugged polymorphic landscape dictated by the terminal domains, high beta-sheet propensity, structural integrity preserved by backbone-based intrachain hydrogen bonds and electrostatic forces, the prominence of the C-terminal domain in the intrachain cross-domain interfaces, and equal participation of hydrophobic and hydrophilic (charged and polar) residues in cross-domain interfaces; and (2) dimerization-modulated characteristics that encompass slower collapsing dynamics, restricted polymorphic landscape, the dominance of side chains in interchain hydrogen bonds, the appearance of the N-terminal domain in the dimer interface, and the prominence of hydrophilic (specifically polar) residues in interchain homo- and cross-domain interfaces. In our work, the ill-known C-terminal domain appears as the most crucial structure-dictating domain, which preferably populates a compact conformation with a high beta-sheet propensity in its isolated state stabilized by intrabackbone hydrogen bonds, and these signatures are comparatively faded in its integrated form. Validation of our simulated observables by a complementary spectroscopic approach on multiple counts ensures the robustness of the computationally predicted features of the TDP-43 aggregation landscape.&lt;/p&gt;
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	Foreign&lt;/p&gt;
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	5&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Tammara, Vaishnavi</style></author><author><style face="normal" font="default" size="100%">Das, Atanu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Decoding the relationship between alzheimer's disease and type-2 diabetes via the protein aggregation prism</style></title><secondary-title><style face="normal" font="default" size="100%">ACS Chemical Neuroscience</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">amylin</style></keyword><keyword><style  face="normal" font="default" size="100%">Amyloid-beta</style></keyword><keyword><style  face="normal" font="default" size="100%">liquid-liquidphase separation</style></keyword><keyword><style  face="normal" font="default" size="100%">Oligomer</style></keyword><keyword><style  face="normal" font="default" size="100%">self vs cross-aggregation</style></keyword><keyword><style  face="normal" font="default" size="100%">unseeded vs seeded aggregation</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2025</style></year><pub-dates><date><style  face="normal" font="default" size="100%">AUG </style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">16</style></volume><pages><style face="normal" font="default" size="100%">3003-3019</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	Alzheimer's disease (AD) and type-2 diabetes (T2D) are two fatal human diseases and have been linked to the aberrant aggregation of two distinct peptides, amyloid-beta (A beta) and human islet amyloid polypeptide (hIAPP), respectively. These two peptide aggregates, even with distal deposition sites (brain and pancreas), act as mutual beneficiaries. We here unveiled the crosstalk in a self-consistent fashion using atomistic simulations by comparing the kinetics and thermodynamics of self- and cross-aggregations of A beta(42) and hIAPP and their modulations by preformed fibrillar templates. Templates (specifically hIAPP) generally accelerate aggregation, alter the relative order of aggregation rates (cross-aggregation &amp;gt; A beta self-aggregation &amp;gt; hIAPP self-aggregation for nontemplated and hIAPP self-aggregation &amp;gt; cross-aggregation &amp;gt; A beta self-aggregation for templated), and flip the mutual impact (hIAPP aggravates A beta aggregation in nontemplated and the reverse in templated). Higher instances of breaking larger aggregates and longer residence times of smaller aggregates decelerate aggregation, whereas interpeptide electrostatics (universal) and hydrogen bonds (templated) assist it. However, the equilibrium aggregability pattern contradicts kinetic rank-ordering, as A beta displays a higher aggregability than hIAPP, templates increase aggregability for both peptides, and A beta's self-aggregability supersedes cross-aggregability, which further surpasses hIAPP's self-aggregability. The equilibrium ensembles encompass polymorphic, nonfibrillar oligomers having substantially reduced alpha-helicity and slight beta-propensity, with both parallel and antiparallel interpeptide orientations, primarily stabilized by electrostatics. A higher equilibrium aggregability means a greater helix-breaking capacity, a bias toward parallel orientation, and a lesser structural polymorphism. Water expulsion from peptide surroundings and distortion of water tetrahedrality prove that aggregation follows the liquid-liquid phase separation (LLPS) model.&lt;/p&gt;
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	Foreign&lt;/p&gt;
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