Mechanisms of domain closure in proteins

Arthur Lesk, Cyrus Chothia

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

Certain enzymes respond to the binding of substrates and coenzymes by the closure of an active site that lies in a cleft between two domains. We have examined the mechanism of the domain closure in citrate synthase, for which atomic co-ordinates are available for "open" and "closed" forms. We show that the mechanism of domain closure involves small shifts and rotations of packed helices within the two domains and at their interface. Large motions of distant segments of the structure are the cumulative effect of the small relative shifts in intervening pairs of packed segments. These shifts are accommodated not by changes in packing but rather by small conformational changes in side-chains. We call this the helix interface shear mechanism of domain closure. The relative movements of packed helices follow the principles suggested by our recent study of insulin. This mechanism of domain closure is quite different from the hinge mechanisms that allow the rigid body movements of domains in immunoglobulins. The large interface between the domains of citrate synthase precludes a simple hinge mechanism for its conformational change. The helix interface shear mechanism of conformational change occurs in other enzymes that contain extensive domain-domain interfaces.

Original languageEnglish (US)
Pages (from-to)175-191
Number of pages17
JournalJournal of Molecular Biology
Volume174
Issue number1
DOIs
StatePublished - Mar 25 1984

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Citrate (si)-Synthase
Coenzymes
Enzymes
Catalytic Domain
Proteins
Insulin
Immunoglobulin Domains

All Science Journal Classification (ASJC) codes

  • Molecular Biology

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Lesk, Arthur ; Chothia, Cyrus. / Mechanisms of domain closure in proteins. In: Journal of Molecular Biology. 1984 ; Vol. 174, No. 1. pp. 175-191.
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Mechanisms of domain closure in proteins. / Lesk, Arthur; Chothia, Cyrus.

In: Journal of Molecular Biology, Vol. 174, No. 1, 25.03.1984, p. 175-191.

Research output: Contribution to journalArticle

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