NUCLEOTIDE DEPENDENT MOVEMENTS OF KINESIN MOTOR DOMAIN: SIMULATED ANNEALING
NUCLEOTIDE DEPENDENT MOVEMENTS OF KINESIN MOTOR DOMAIN: SIMULATED ANNEALING
批准号:
6122387
负责人:
WILLY R WRIGGERS
金额:
$1.36万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-08-01 至 1999-07-31
中文摘要
ATP结合的驱动蛋白运动域的结构已被发现
预测和构象差异相对于已知的
鉴定了蛋白质的ADP结合形式,* 如在
参考文献[96]。 这些差异应归因于
产生ATP水解的力。 候选的ATP驱动蛋白结构是
通过模拟退火获得,通过放置ATP
ADP-驱动蛋白的晶体结构中的γ-磷酸,
原子间距离约束。 这种约束的选择是
基于诱变实验,将Gly 234鉴定为
γ-磷酸盐敏感残基,以及结构上的
驱动蛋白与同源ncd马达和G
proteins. 核苷酸依赖构象的预测
差异揭示了核苷酸之间的变构偶联
口袋和驱动蛋白的微管结合位点。 相互作用
ATP与Gly 234和Ser 202触发运动中的结构变化
结构域,作为驱动蛋白的变构修饰剂的核苷酸,
微管结合状态。 我们认为,在ATP存在的情况下,
驱动蛋白的推定微管结合区(L 8,L12,L11,α 4,
α 5和α 6)形成形状与所述表面互补的面,
微管表面 在ADP存在下,微管结合
面采用相对于ATP结合形式更凸的形状,
降低了驱动蛋白对微管的亲和力。
英文摘要
The structure of an ATP-bound kinesin motor domain has been
predicted and conformational differences relative to the known
ADP-bound form of the protein were identified,* as reported in
reference [96]. The differences should be attributed to
force-producing ATP hydrolysis. Candidate ATP-kinesin structures were
obtained by simulated annealing, by placement of the ATP
gamma-phosphate in the crystal structure of ADP-kinesin, and by
inter-atomic distance constraints. The choice of such constraints was
based on mutagenesis experiments, which identified Gly234 as one of
the gamma-phosphate sensing residues, as well as on structural
comparison of kinesin with the homologous ncd motor and with G
proteins. The prediction of nucleotide-dependent conformational
differences reveals an allosteric coupling between the nucleotide
pocket and the microtubule binding site of kinesin. Interactions of
ATP with Gly234 and Ser202 trigger structural changes in the motor
domain, the nucleotide acting as an allosteric modifier of kinesin's
microtubule-binding state. We suggest that in the presence of ATP
kinesin's putative microtubule binding regions (L8, L12, L11, alpha4,
alpha5 and alpha6) form a face complementary in shape to the
microtubule surface. In the presence of ADP, the microtubule binding
face adopts a more convex shape relative to the ATP-bound form,
reducing kinesin's affinity to the microtubule.
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项目类别:
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资助金额:$31.27万
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依托单位:
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批准号:6295247
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项目类别:
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资助金额:$2.31万
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财政年份:1999
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负责人:WILLY R WRIGGERS
-
依托单位:
NUCLEOTIDE DEPENDENT MOVEMENTS OF KINESIN MOTOR DOMAIN: SIMULATED ANNEALING
-
批准号:6295249
-
项目类别:
-
资助金额:$2.31万
-
财政年份:1999
-
负责人:WILLY R WRIGGERS
-
依托单位:
STRUCTURE & DYNAMICS OF CALMODULIN IN SOLUTION: MUSCLE CONTRACTION
-
批准号:6122385
-
项目类别:
-
资助金额:$1.36万
-
财政年份:1998
-
负责人:WILLY R WRIGGERS
-
依托单位:
NUCLEOTIDE DEPENDENT MOVEMENTS OF KINESIN MOTOR DOMAIN: SIMULATED ANNEALING
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批准号:6282422
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项目类别:
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资助金额:$2.31万
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财政年份:1998
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负责人:WILLY R WRIGGERS
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依托单位:
STRUCTURE & DYNAMICS OF CALMODULIN IN SOLUTION: MUSCLE CONTRACTION
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批准号:6282420
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项目类别:
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资助金额:$2.31万
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财政年份:1998
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负责人:WILLY R WRIGGERS
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批准号:6253389
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资助金额:$7.78万
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财政年份:1997
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负责人:WILLY R WRIGGERS
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批准号:6253398
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海外基金