Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39.

Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39. Research Abstract Details 

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Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39. Abstract Text:

Alison Grinthal,Guido Guidotti,

CD39 can exist in at least two distinct functional states depending on the presence and intact membrane integration of its two transmembrane helices. In native membranes, the transmembrane helices undergo dynamic rotational motions that are required for enzymatic activity and are regulated by substrate binding. In this study, we show that bilayer mechanical properties regulate conversion between the two enzymatic functional states by modulating transmembrane helix dynamics. Alteration of membrane properties by insertion of cone-shaped or inverse cone-shaped amphiphiles or by cholesterol removal switches CD39 to the same enzymatic state that removal or solubilization of the transmembrane domains does. The same membrane alterations increase the propensity of both transmembrane helices to rotate within the packed structure, resulting in a structure with greater mobility but not an altered primary conformation. Membrane alteration also abolishes the ability of the substrate to stabilize the helices in their primary conformation, indicating a loss of coupling between substrate binding and transmembrane helix dynamics. Removal of either transmembrane helix mimics the effect of membrane alteration on the mobility and substrate sensitivity of the remaining helix, suggesting that the ends of the extracellular domain have intrinsic flexibility. We suggest that a mechanical bilayer property, potentially elasticity, regulates CD39 by altering the balance between the stability and flexibility of its transmembrane helices and, in turn, of its active site.

Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39. Publishing Authors By Initials

A Grinthal,G Guidotti,

For similar chemical actions and uses: specialty uses of chemicals: surface-active agents research abstracts see: chemical actions and uses: specialty uses of chemicals: surface-active agents research

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Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Biochemistry

VOLUME: 46

Page Numbers: 279-90

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 9

MONTH: Jan

YEAR: 2007

Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39. Keywords Mesh Terms:

KEYWORDS: Surface-Active Agents

MESH TERMS: metabolism

Chemical & Substance for Abstract: Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39. Information

Substance Name: CD39 antigen

Registry Number: EC 3.6.1.5

Grant and Affiliation Information for Bilayer mechanical properties regulate the transmembrane helix mobility and enzymatic state of CD39.

AFFILIATION: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. agrinth@fas.harvard.edu

Country: United States

AGENCY: United States NHLBI

GRANT: HL08893

ACRONYM: HL

MEDLINETA: Biochemistry

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