龙加福
1 神经系统中参与信号传导的蛋白-蛋白及蛋白-脂的相互作用;2 信号蛋白结构与功能的关系;3 与人类重大疾病相关蛋白的作用机理。
个性化签名
- 姓名:龙加福
- 目前身份:
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学术头衔:
博士生导师, 教育部“新世纪优秀人才支持计划”入选者
- 职称:-
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学科领域:
生物化学
- 研究兴趣:1 神经系统中参与信号传导的蛋白-蛋白及蛋白-脂的相互作用;2 信号蛋白结构与功能的关系;3 与人类重大疾病相关蛋白的作用机理。
龙加福,男,现任南开大学生命科学学院教授,博士生导师,校特聘教授,2007年度教育部新世纪优秀人才。1999年毕业于南开大学生命科学学院生物化学及分子生物学系,获得学士学位,同年9月进入香港科技大学生物化学系学习,2004年8月获得香港科技大学生物化学博士学位。2004年9月至2006年11月于香港科技大学生物化学系从事博士后研究。
学科方向:神经系统中参与信号传导的蛋白-蛋白及蛋白-脂的相互作用,信号蛋白结构与功能的关系。
主要研究方向:1 神经系统中参与信号传导的蛋白-蛋白及蛋白-脂的相互作用;2 信号蛋白结构与功能的关系;3 与人类重大疾病相关蛋白的作用机理。
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成果数
7
龙加福, Jiafu Long, †, Zhiyi Wei†, Wei Feng, Cong Yu, Yan-xiang Zhao* and Mingjie Zhang*
J. Mol. Biol. (2008) 375, 1457-1468,-0001,():
-1年11月30日
The scaffold protein GRIP1 (glutamate receptor interacting protein 1) binds to and regulates both the trafficking and membrane organization of a large number of transmembrane proteins. Mutation of GRIP1 in mice displays essentially the same phenotype of the mutations of Fras1 or Frem2, which are the animal models of the human genetic disorder Fraser syndrome. However, the molecular basis governing the interaction between GRIP1 and Fras1/Frem2 is unknown. Here, we show that interaction between Fras1 and GRIP1 requires the first two PDZ domains (PDZ1 and PDZ2) to be connected in tandem, as the folding of PDZ1 strictly depends on the covalent attachment of PDZ2. The crystal structure of GRIP1 PDZ12 in complex with the Fras1 C-terminal peptide reveals that the PDZ12 tandem forms a supramodule in which only the peptide-binding groove of PDZ1 is bound with the Fras1 peptide. The GRIP1 PDZ12/Fras1 peptide complex not only provides a mechanistic explanation of the link between GRIP1 and the Fraser syndrome but may also serve as a foundation for searching for potential mutations in GRIP1 that could lead to the Fraser syndrome.
GRIP1, PDZ tandem, protein trafficking, Fraser syndrome, Fras1
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龙加福, Jia-Fu Long, Wei Feng, Rui Wang, Ling-Nga Chan, Fanny C F Ip, Jun Xia, Nancy Y Ip & Mingjie Zhang
NATURE STRUCTURAL & MOLECULAR BIOLOGY VOLUME 12 NUMBER 8 AUGUST 2005,-0001,():
-1年11月30日
Members of the X11/Mint family of multidomain adaptor proteins are composed of a divergent N terminus, a conserved PTB domain and a pair of C-terminal PDZ domains. Many proteins can interact with the PDZ tandem of X11 proteins, although the mechanism of such interactions is unclear. Here we show that the highly conserved C-terminal tail of X11a folds back and inserts into the target-binding groove of the first PDZ domain. The binding of this tail occludes the binding of other target peptides. This autoinhibited conformation of X11 requires that the two PDZ domains and the entire C-terminal tail be covalently connected to form an integral structural unit. The autoinhibited conformation of the X11 PDZ tandem provides a mechanistic explanation for the unique target-binding properties of the protein and hints at potential regulatory mechanisms for the X11-target interac-tions.
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龙加福, Jing Yan, , Wenyu Wen, Weiguang Xu, Jia-fu Long, Marvin E Adams, Stanley C Froehner and Mingjie Zhang, *
The EMBO Journal (2005) 24, 3985-3995,-0001,():
-1年11月30日
Pleckstrin homology (PH) domains play diverse roles in cytoskeletal dynamics and signal transduction. Split PH domains represent a unique subclass of PH domains that have been implicated in interactions with complementary partial PH domains ‘hidden’ in many proteins. Whether partial PH domains exist as independent structural units alone and whether two halves of a split PH domain can fold together to form an intact PH domain are not known. Here, we solved the structure of the PHN-PDZ-PHC tandem of a-syntrophin. The split PH domain of a-syntrophin adopts a canonical PH domain fold. The isolated partial PH domains of a-syntrophin, although completely unfolded, remain soluble in solution. Mixing of the two isolated domains induces de novo folding and yields a stable PH domain. Our results demonstrate that two complementary partial PH domains are capable of binding to each other to form an intact PH domain. We further showed that the PHN-PDZ-PHC tandem forms a functionally distinct supramodule, in which the split PH domain and the PDZ domain function synergistically in binding to inositol phospholipids.
lipid binding, PDZ domain, split PH domain, supramodule, syntrophin
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龙加福, Wei Feng*, Jia-fu Long*, and Mingjie Zhang†
PNAS, May 10, 2005, vol. 102, no.19, 6861-6866,-0001,():
-1年11月30日
Initially identified in Caenorhabditis elegans Lin-2 and Lin-7, L27 domain is a protein–protein interaction domain capable of organizing scaffold proteins into supramolecular assemblies by formation of heteromeric L27 domain complexes. L27 domain-mediated protein assemblies have been shown to play essential roles in cellular processes including asymmetric cell division, establishment and maintenance of cell polarity, and clustering of receptors and ion channels. The structural basis of L27 domain heteromeric complex assembly is controversial. We determined the high-resolution solution structure of the prototype L27 domain complex formed by mLin-2 and mLin-7 as well as the solution structure of the L27 domain complex formed by Patj and Pals1. The structures suggest that a tetrameric structure composed of two units of heterodimer is a general assembly mode for cognate pairs of L27 domains. Structural analysis of the L27 domain complex structures further showed that the central four-helix bundles mediating tetramer assembly are highly distinct between different pairs of L27 domain complexes. Biochemical studies revealed that the C-terminal -helix responsible for the formation of the central helix bundle is a critical specificity determinant for each L27 domain in choosing its binding partner. Our results provide a unified picture for L27 domain-mediated protein-protein interactions.
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【期刊论文】The tetrameric L27 domain complex as an organization platform for supramolecular assemblies
龙加福, Wei Feng, , Jia-Fu Long, Jing-Song Fan, Tetsuya Suetake & Mingjie Zhang
NATURE STRUCTURAL & MOLECULAR BIOLOGY VOLUME 11 NUMBER 5 MAY 2004,-0001,():
-1年11月30日
L27 domain, initially identified in the Caenorhabditis elegans Lin-2 and Lin-7 proteins, is a protein interaction module that exists in a large family of scaffold proteins. The domain can function as an organization center of large protein assemblies required for establishment and maintenance of cell polarity. We have solved the high-resolution NMR structure of a tetrameric complex of L27 domains containing two SAP97-mLin-2 L27 domain heterodimers. Each L27 domain contains three-helices. The first two helices of each domain are packed together to form a four-helical bundle in the hetero- dimer. The third helix of each L27 domain forms another four-helical bundle that assembles the two heterodimers into a tetramer. The structure of the complex provides a mechanistic explanation for L27 domain-mediated polymerization of scaffold proteins, a process that is crucial for the assembly of supramolecular complexes in asymmetric cells.
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龙加福, Po-yan Cheung‡, Yi Zhang§, Jiafu Long‡, Shengcai Lin‡, Mingjie Zhang‡, Yong Jiang¶, and Zhenguo Wu‡
THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 279, No.44, Issue of October 29, pp. 45308-45311, 2004,-0001,():
-1年11月30日
To look for regulators of the mitogen-activated protein kinase (MAPK) kinase 6 (MKK6), a yeast two-hybrid screen was initiated using MKK6 as bait. p150Glued dynactin, a key component of the cytoplasmic dynein-dynactin motor complex, was found to specifically interact with MKK6 and its close homologue MKK3. Silencing of p150Glued expression by small interference RNA reduced the stimulus-induced phosphorylation of MKK3/6 and p38 MAPKs. The similar adverse effect was also seen when the cytoplasmic dynein motor was disrupted by other means. Like p150Glued, MKK3/6 directly associate with microtubules. Disruption of microtubules prior to cell stimulation specifically inhibits the stimulus-induced phosphorylation of both MKK3/6 and p38 MAPKs. Our unexpected findings reveal a specific requirement for p150Glued/dynein/functional microtubules in activation of MKK3/6 and p38 MAPKs in vivo.
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龙加福, Jia-Fu Long, Hidehito Tochio, Ping Wang, Jing-Song Fan Carlo Sala, Martin Niethammer, Morgan Sheng* and Mingjie Zhang*
J. Mol. Biol. (2003) 327, 203-214,-0001,():
-1年11月30日
PDZ domain proteins play critical roles in binding, clustering and subcellular targeting of membrane receptors and ion channels. PDZ domains in multi-PDZ proteins often are arranged in groups with highly conserved spacing and intervening sequences; however, the functional significance of such tandem arrangements of PDZs is unclear. We have solved the three-dimensional structure of the first two PDZ domains of postsynaptic density protein-95 (PSD-95 PDZ1 and PDZ2), which are closely linked to each other in the PSD-95 family of scaffold proteins. The two PDZs have limited freedom of rotation and their C-terminal peptide-binding grooves are aligned with each other with an orientation preference for binding to pairs of C termini extending in the same direction. Increasing the spacing between PDZ1 and PDZ2 resulted in decreased binding between PDZ12 and its dimeric targets. The same mutation impaired the functional ability of PSD-95 to cluster Kv1.4 potassium channels in heterologous cells. The data presented provide a molecular basis for preferential binding of PSD-95 to multimeric membrane proteins with appropriate C-terminal sequences.
PSD-95, PDZ domain, modular structure, receptor clustering, scaffolding protein
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