FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W276386931> ?p ?o ?g. }

• W276386931 abstract "Title: Intermediates and the Folding of Proteins L and G Authors: Scott Brown † and Teresa Head-Gordon* Department of Bioengineering University of California, Berkeley Berkeley, CA 94720 Keywords: Intermediates, Kinetic mechanism, Protein L and G, minimalist model, protein folding Abstract. We use a minimalist protein model, in combination with a sequence design strategy, to determine differences in primary structure for proteins L and G that are responsible for the two proteins folding through distinctly different folding mechanisms. We find that the folding of proteins L and G are consistent with a nucleation-condensation mechanism, each of which is described as helix-assisted β−1 and β−2 hairpin formation, respectively. We determine that the model for protein G exhibits an early intermediate that precedes the rate-limiting barrier of folding and which draws together misaligned secondary structure elements that are stabilized by hydrophobic core contacts involving the third β−strand, and presages the later transition state in which the correct strand alignment of these same secondary structure elements is restored. Finally the validity of the targeted intermediate ensemble for protein G was analyzed by fitting the kinetic data to a two-step first order reversible reaction, proving that protein G folding involves an on-pathway early intermediate, and should be populated and therefore observable by experiment. Current address: Abbott Laboratories, 1401 Sheridan Road, North Chicago, Illinois 60064-4000 Introduction While thermodynamics and kinetics of small proteins that fold via a two-state manner are reasonably well-understood (Daggett & Fersht, 2003a; Gruebele, 2002b; Myers & Oas, 2002), understanding how (and why!) proteins fold through intermediates will be especially relevant for larger proteins, more complicated topologies, and their possible connection to aggregation processes that are responsible for disease(Speed et al., 1997). Some of the open questions surrounding intermediates include the detection of the so-called “hidden” intermediates by kinetic experiments, whether intermediates can occur earlier than the rate-limiting step in folding, i.e. do free energy barriers that precede the rate-limiting nucleation barrier of the folding reaction exist, and if they are “off-pathway” and therefore obstruct the functionally important progress of folding (Gruebele, 2002a; Ozkan et al., 2002; Qin et al., 2002; Sanchez & Kiefhaber, 2003a). This work examines the question of intermediates by simulating the folding of two members of the ubiquitin fold class, Ig-binding proteins L and G. Proteins L and G make excellent targets for theoretical study as their folding attributes have been extensively studied by experiment (Gu et al., 1997; Gu et al., 1995; Kim et al., 2000; Krantz et al., 2002; McCallister et al., 2000; Park et al., 1997; Park et al., 1999; Scalley et al., 1997). These two single-domain proteins have little sequence identity and but identical fold topologies, consisting of a central α−helix packed against a four-strand β−sheet composed of two β−hairpins. Experimental evidence indicates that protein L folds in a two-state manner through a transition state ensemble involving a native-like β- hairpin 1, and largely disrupted β-hairpin 2(Gu et al., 1997; Kim et al., 2000; Scalley et al., 1997). Protein G on the other hand, folds through a possible early intermediate (Park et al., 1997; Park et al., 1999; Speed et al., 1997), followed by a rate-limiting step that involves formation of β-hairpin 2. They therefore provide a perfect contrast to understand features that give rise to protein folding intermediates, while controlling for size and topology. There have been a number of recent simulations of coarse-grained models of proteins L and/or G using different forms of minimalist models(Head-Gordon & Brown, 2003). Shimada and Shakhnovich have used ensemble dynamics to characterize the kinetics of protein G using an all-atom Gō potential(Shimada & Shakhnovich, 2002). Karanicolas and Brooks use a Gō potential bead model supplemented with sequence-dependent MJ statistical potentials to differentiate the folding of G and L(Karanicolas & Brooks, 2002). They found the origin of asymmetry in the folding of protein L and G to be in concurrence with that found by Nauli and co-workers (Nauli et al., 2001), who used a computer-based design strategy to reengineer the protein G sequence to include more stabilizing interactions for the first beta-hairpin turn, producing a protein more faithful to the mechanism of folding for protein L. Our recent work, inspired by early efforts of Thirumalai and co-workers (Guo & Thirumalai, 1996; Guo et al., 1992; Honeycutt & Thirumalai, 1990), develops physics-based potentials which make the connection between free energy landscapes and amino acid sequence, allowing us to engineer sequences that" @default.
• W276386931 created "2016-06-24" @default.
• W276386931 creator A5037869820 @default.
• W276386931 creator A5056814590 @default.
• W276386931 date "2008-05-16" @default.
• W276386931 modified "2023-09-27" @default.
• W276386931 title "Intermediates and the folding of proteins L and G" @default.
• W276386931 cites W1499741065 @default.
• W276386931 cites W1505900198 @default.
• W276386931 cites W1535441016 @default.
• W276386931 cites W1561923743 @default.
• W276386931 cites W1563805057 @default.
• W276386931 cites W1570122994 @default.
• W276386931 cites W1588812136 @default.
• W276386931 cites W1959078926 @default.
• W276386931 cites W1968291593 @default.
• W276386931 cites W1970440715 @default.
• W276386931 cites W1977482735 @default.
• W276386931 cites W1979908355 @default.
• W276386931 cites W1993321394 @default.
• W276386931 cites W1997621425 @default.
• W276386931 cites W2005865331 @default.
• W276386931 cites W2016019576 @default.
• W276386931 cites W2021985383 @default.
• W276386931 cites W2023083682 @default.
• W276386931 cites W2029927731 @default.
• W276386931 cites W2034278689 @default.
• W276386931 cites W2044967926 @default.
• W276386931 cites W2048268480 @default.
• W276386931 cites W2051039246 @default.
• W276386931 cites W2052124922 @default.
• W276386931 cites W2053315180 @default.
• W276386931 cites W2064589158 @default.
• W276386931 cites W2071075252 @default.
• W276386931 cites W2079010479 @default.
• W276386931 cites W2079697713 @default.
• W276386931 cites W2079884830 @default.
• W276386931 cites W2079911245 @default.
• W276386931 cites W2081713822 @default.
• W276386931 cites W2086975932 @default.
• W276386931 cites W2089597488 @default.
• W276386931 cites W2091323678 @default.
• W276386931 cites W2091640762 @default.
• W276386931 cites W2099804970 @default.
• W276386931 cites W2107165577 @default.
• W276386931 cites W2115005877 @default.
• W276386931 cites W2137583795 @default.
• W276386931 cites W2138169394 @default.
• W276386931 cites W2152326664 @default.
• W276386931 cites W2156042112 @default.
• W276386931 cites W2158476854 @default.
• W276386931 cites W2165768701 @default.
• W276386931 cites W2169632544 @default.
• W276386931 hasPublicationYear "2008" @default.
• W276386931 type Work @default.
• W276386931 sameAs 276386931 @default.
• W276386931 citedByCount "1" @default.
• W276386931 crossrefType "journal-article" @default.
• W276386931 hasAuthorship W276386931A5037869820 @default.
• W276386931 hasAuthorship W276386931A5056814590 @default.
• W276386931 hasConcept C119599485 @default.
• W276386931 hasConcept C12554922 @default.
• W276386931 hasConcept C127413603 @default.
• W276386931 hasConcept C162203774 @default.
• W276386931 hasConcept C185592680 @default.
• W276386931 hasConcept C188198153 @default.
• W276386931 hasConcept C204328495 @default.
• W276386931 hasConcept C2776545253 @default.
• W276386931 hasConcept C47701112 @default.
• W276386931 hasConcept C55493867 @default.
• W276386931 hasConcept C78519656 @default.
• W276386931 hasConcept C8010536 @default.
• W276386931 hasConcept C86803240 @default.
• W276386931 hasConceptScore W276386931C119599485 @default.
• W276386931 hasConceptScore W276386931C12554922 @default.
• W276386931 hasConceptScore W276386931C127413603 @default.
• W276386931 hasConceptScore W276386931C162203774 @default.
• W276386931 hasConceptScore W276386931C185592680 @default.
• W276386931 hasConceptScore W276386931C188198153 @default.
• W276386931 hasConceptScore W276386931C204328495 @default.
• W276386931 hasConceptScore W276386931C2776545253 @default.
• W276386931 hasConceptScore W276386931C47701112 @default.
• W276386931 hasConceptScore W276386931C55493867 @default.
• W276386931 hasConceptScore W276386931C78519656 @default.
• W276386931 hasConceptScore W276386931C8010536 @default.
• W276386931 hasConceptScore W276386931C86803240 @default.
• W276386931 hasLocation W2763869311 @default.
• W276386931 hasOpenAccess W276386931 @default.
• W276386931 hasPrimaryLocation W2763869311 @default.
• W276386931 hasRelatedWork W1507973922 @default.
• W276386931 hasRelatedWork W166887480 @default.
• W276386931 hasRelatedWork W1937641960 @default.
• W276386931 hasRelatedWork W1965341752 @default.
• W276386931 hasRelatedWork W1978248762 @default.
• W276386931 hasRelatedWork W2000531275 @default.
• W276386931 hasRelatedWork W2014460723 @default.
• W276386931 hasRelatedWork W2019746877 @default.
• W276386931 hasRelatedWork W2029077904 @default.
• W276386931 hasRelatedWork W2036226858 @default.
• W276386931 hasRelatedWork W2048370177 @default.

• next