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Membrane perforation and related str...

Myers, Kimberly Shawnta.

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Membrane perforation and related structural transitions by reovirus particles.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Membrane perforation and related structural transitions by reovirus particles./
作者:	Myers, Kimberly Shawnta.
面頁冊數:	201 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2358.
Contained By:	Dissertation Abstracts International67-05B.
標題:	Biology, Microbiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3217834
ISBN:	9780542693519

Membrane perforation and related structural transitions by reovirus particles.
Myers, Kimberly Shawnta.

Membrane perforation and related structural transitions by reovirus particles. - 201 p.

Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2358.

Thesis (Ph.D.)--Harvard University, 2006.

The mechanism by which the large, nonenveloped reoviruses disrupt host cell membranes and deliver a particle activated for transcription into the cytoplasm remains largely undefined. A conformational transition from the disassembly intermediate known as the ISVP to the newly characterized disassembly intermediate termed the ISVP* is associated with the ability of reoviruses to disrupt membranes as assayed by red blood cell lysis (hemolysis). In the following, red blood cells (RBCs) were used as surrogate membranes in studies to define the conditions that influence the rate of the ISVP to ISVP* conformational transition and subsequent membrane disruption. The concentration of ISVPs, pH, and the presence and identity of monovalent cations influence the rate of the ISVP to ISVP* conformational transition. However, the rate of the transition and the maximum levels of hemolysis achieved are uninfluenced by RBC concentration and calcium-dependent RBC membrane repair. The ISVP to ISVP* conformational transition obeys a second-order kinetic model, arguing that particle: particle or particle: released component interactions drive the conformational transition toward completion. Further, the conformational transition obeys the Arrhenius relationship for temperature dependence, arguing that ISVPs are metastable particles that overcome an energy barrier to undergo the conformational transition to the ISVP*.

ISBN: 9780542693519Subjects--Topical Terms:

1017734
Biology, Microbiology.

Membrane perforation and related structural transitions by reovirus particles.
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245 1 0 $a Membrane perforation and related structural transitions by reovirus particles.
300 $a 201 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-05, Section: B, page: 2358.
500 $a Adviser: Max L. Nibert.
502 $a Thesis (Ph.D.)--Harvard University, 2006.
520 $a The mechanism by which the large, nonenveloped reoviruses disrupt host cell membranes and deliver a particle activated for transcription into the cytoplasm remains largely undefined. A conformational transition from the disassembly intermediate known as the ISVP to the newly characterized disassembly intermediate termed the ISVP* is associated with the ability of reoviruses to disrupt membranes as assayed by red blood cell lysis (hemolysis). In the following, red blood cells (RBCs) were used as surrogate membranes in studies to define the conditions that influence the rate of the ISVP to ISVP* conformational transition and subsequent membrane disruption. The concentration of ISVPs, pH, and the presence and identity of monovalent cations influence the rate of the ISVP to ISVP* conformational transition. However, the rate of the transition and the maximum levels of hemolysis achieved are uninfluenced by RBC concentration and calcium-dependent RBC membrane repair. The ISVP to ISVP* conformational transition obeys a second-order kinetic model, arguing that particle: particle or particle: released component interactions drive the conformational transition toward completion. Further, the conformational transition obeys the Arrhenius relationship for temperature dependence, arguing that ISVPs are metastable particles that overcome an energy barrier to undergo the conformational transition to the ISVP*.
520 $a In a second study, we begin to define the molecular interactions that regulate the ISVP to ISVP* conversion. Heat-treated ISVPs undergo a conformational transition that is similar, or identical, to the ISVP to ISVP* conformational conversion. We selected and characterized reovirus heat-resistant mutants from ISVPs. All heat-resistant clones have mutations in the membrane-penetration protein mu1. Most mutations are surface-exposed, making inter- and intra-trimeric contacts predominantly in the "top" jelly-roll containing domain of the trimeric mu1 protein. A subset of heat-resistant mutants was chosen for further analysis. While the mutants display minimal growth defects, all display defects in undergoing the ISVP to ISVP* conformational transition, as well as defects in the ability to hemolyze RBCs. For at least one heat-resistant mutant, the hemolysis defect can be overcome at particle concentrations that exceed those generally required by wild-type particles to hemolyze RBCs.
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791 $a Ph.D.
792 $a 2006
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