Structural and dynamic characterization of a neuron-specific protein kinase C substrate, neurogranin

	Structural and dynamic characterization of a neuron-specific protein kinase C substrate, neurogranin
	Ran, XY; Miao, HH; Sheu, FS; Yang, D
刊名	BIOCHEMISTRY
	2003
卷号	42 期号:17 页码:5143-5150
通讯作者	Yang, D (reprint author), Natl Univ Singapore, Dept Sci Biol, 14 Sci Dr 4, Singapore 117543, Singapore.,
英文摘要	Neurogranin/RC3 is a neuron-specific, Ca2+-sensitive calmodulin binding protein and a specific protein kinase C substrate. Neurogranin may function to regulate calmodulin levels at specific sites in neurons through phosphorylation at serine residue within its IQ motif, oxidation outside the IQ motif, or changes in local cellular Call concentration. To gain insight into the functional role of neurogranin in the regulation of calmodulin-dependent activities, we investigated the structure and dynamics of a full-length rat neurogranin protein with 78 amino acids using triple resonance NMR techniques. In the absence of calmodulin or PKC, neurogranin exists in an unfolded form as evidenced by high backbone mobility and the absence of long-range nuclear Overhauser effect (NOE). Analyses of the chemical shifts C-13(alpha), C-13(beta), and H-1(alpha) reveal the presence of a local a.-helical structure for the region between residues G25-A42. Three-bond 1H(N)-H-1(alpha). coupling constants support the finding that the sequence between residues G25 and A42 populates a non-native helical structure in the unfolded neurogranin. Homonuclear NOE results are consistent with the conclusions drawn from chemical shifts and coupling constants. N-15 relaxation data indicate motional restrictions on a nanosecond time scale in the region from D15 to S48. Spectral densities and order parameters data further confirm that the unfolded neurogranin exists in conformation with residual secondary structures. The medium mobility of the nascent helical region may help to reduce the entropy loss when neurogranin binds to its targets, but the complex between neurogranin and calmodulin is not stable enough for structural determination by NMR. Calmodulin titration of neurogranin indicates that residues D15-G52 of neurogranin undergo significant structural changes upon binding to calmodulin.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	NUCLEAR-MAGNETIC-RESONANCE ; CALMODULIN-BINDING DOMAIN ; NITRIC-OXIDE MODIFICATION ; RAT-BRAIN NEUROGRANIN ; NMR CHEMICAL-SHIFTS ; CONFORMATIONAL ENTROPY ; NEUROMODULIN GAP-43 ; SECONDARY STRUCTURE ; BACKBONE DYNAMICS ; DEPENDENT TARGET
收录类别	SCI
语种	英语
WOS记录号	WOS:000182621700043
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2380]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Ran, XY,Miao, HH,Sheu, FS,et al. Structural and dynamic characterization of a neuron-specific protein kinase C substrate, neurogranin[J]. BIOCHEMISTRY,2003,42(17):5143-5150.
APA	Ran, XY,Miao, HH,Sheu, FS,&Yang, D.(2003).Structural and dynamic characterization of a neuron-specific protein kinase C substrate, neurogranin.BIOCHEMISTRY,42(17),5143-5150.
MLA	Ran, XY,et al."Structural and dynamic characterization of a neuron-specific protein kinase C substrate, neurogranin".BIOCHEMISTRY 42.17(2003):5143-5150.