CHARACTERIZATION OF THE NONSTRUCTURAL PROTEINS OF ADENO ASSOCIATED VIRUS
CHARACTERIZATION OF THE NONSTRUCTURAL PROTEINS OF ADENO ASSOCIATED VIRUS
批准号:
2576788
负责人:
R KOTIN
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
腺相关病毒AAV的四种非结构蛋白(Rep)
英文摘要
The four non-structural proteins (Rep) of adeno-associated virus, AAV,
are encoded by a single open reading frame, the rep gene, and differ from
each other by utilization of an downstream promoter and excision of an
intron. The two larger Rep proteins function as replication origin
binding and initiation proteins and are required for viral DNA synthesis.
Previously, we have demonstrated that the two larger Rep proteins, Rep
68 and Rep 78, are DNA binding proteins that recognize a sequence motif,
the prototype is the GAGC repeat within the AAV inverted terminal repeat
(ITR). The DNA binding ability of Rep proteins may have explained the
regulatory effects of Rep proteins on gene expression that has been
observed by several laboratories. However, this effect appears to be
independent of the presence of a canonical Rep binding site within the
regulatory region of the transcribed gene. Other cellular phenotypes
associated with Rep 68 or Rep 78 expression include: loss of viability,
inhibition of cell division, and inhibition of transformation by viral
oncogenes. These effects may be induced by Rep association with a
cellular protein.
Domains of Rep proteins that are necessary for Rep oligomerization have
been reported previously. However, the residues that are specifically
required for these interactions have not been defined. In order to
identify which residues are involved with inter-protein interactions, we
have made a series of mutations altering a single residue Rep 78. Our
results with analytical chromatography demonstrate that Rep 78 or Rep 68
forms a complex with properties consistent with a hexamer similar to
other DNA helicase complexes. Defining how a polypeptide interacts with
other proteins enables us to generalize and predict what other
interactions may occur. Binding of Rep to epitopes displayed on
bacteriophage has resulted in selection of clones with a commonly
repeated motif. We are in the process of determining whether cellular
proteins containing these epitopes interact with Rep 78 and if so, what
are the effects on the cellular processes.
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CHARACTERIZATION OF THE NONSTRUCTURAL PROTEINS OF ADENO ASSOCIATED VIRUS
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批准号:6162699
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:R KOTIN
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依托单位:
ADENO-ASSOCIATED VIRUS IN VITRO INTEGRATION AND REPLICATION
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批准号:5203534
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:R KOTIN
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依托单位:
RECOMBINANT ADENO ASSOCIATED VIRUS
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批准号:2576791
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:R KOTIN
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依托单位:
AAV REP PROTEINS AND TARGETED INTEGRATION
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批准号:3757654
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:R KOTIN
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依托单位:
RECOMBINANT ADENO ASSOCIATED VIRUS
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批准号:6162701
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:R KOTIN
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依托单位:
RECOMBINANT ADENO-ASSOCIATED VIRUS
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批准号:5203536
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:R KOTIN
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依托单位:
海外基金