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Titolo:
Effects of core mutations on the folding of a beta-sheet protein: Implications for backbone organization in the I-State
Autore:
Lorch, M; Mason, JM; Clarke, AR; Parker, MJ;
Indirizzi:
Univ Bristol, Sch Med Sci, Dept Biochem, Bristol BS8 1TD, Avon, England Univ Bristol Bristol Avon England BS8 1TD Bristol BS8 1TD, Avon, England
Titolo Testata:
BIOCHEMISTRY
fascicolo: 4, volume: 38, anno: 1999,
pagine: 1377 - 1385
SICI:
0006-2960(19990126)38:4<1377:EOCMOT>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
HELIX-FORMING TENDENCIES; ALPHA-HELIX; AMINO-ACIDS; GLOBULAR-PROTEINS; THERMODYNAMIC SCALE; KINETIC-ANALYSIS; STABILITY; PROPENSITIES; PEPTIDES; MODEL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Lorch, M UnivEnglandl, Sch Med Sci, Dept Biochem, Univ Walk, Bristol BS8 1TD, Avon, Univ Bristol Univ Walk Bristol Avon England BS8 1TD S8 1TD, Avon,
Citazione:
M. Lorch et al., "Effects of core mutations on the folding of a beta-sheet protein: Implications for backbone organization in the I-State", BIOCHEM, 38(4), 1999, pp. 1377-1385

Abstract

A series of core mutations were introduced into beta-strand segments of animmunoglobulin fold (the isolated first domain of CD2, CD2.d1) to examine their influence on the rapidly formed intermediate state (I-state) which transiently accumulates in the folding reaction [Parker, M. J., and Clarke, A. R. (1997) Biochemistry 36, 5786-5794]. The residue changes were chemically conservative, each representing the removal of one or two methylene groups from aliphatic side chains. Predictably, the mutations destabilize the folded state with respect to the unfolded state by about 1.1 +/- 0.7 kcal mol(-1) per methylene group removed. However, when the folding reaction is dissected by transient kinetic analysis into its component steps, six out of the nine mutations lead to a stabilization of the I-state. The direction andmagnitude of these effects on the global stability of the transient intermediate are well correlated with changes in secondary structure propensity occasioned by the substitutions. The results show that, although side chain interactions are extremely weak in this early phase of folding, the beta-strand conformation of the polypeptide chain is established. In the next phase of the reaction, the rate-limiting transition state is attained by the formation of a tightly localized hydrophobic nucleus which includes residues V30, I18, and V78. Interestingly, in almost all immunoglobulin domains of extracellular proteins, the latter pair are cysteine residues which form a disulfide bridge.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 09:14:47