1H NMR Structural Characterization of a Nonmitogenic, Vasodilatory, Ischemia-Protector and Neuromodulatory Acidic Fibroblast Growth Factor

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• 作者：Rosa M. Lozano ; Antonio Pineda-Lucena ; Carlos Gonzalez ; M. &Aacute ; ngeles Jimé ; nez ; Pedro Cuevas ; Mariano Redondo-Horcajo ; Jesú ; s M. Sanz ; Manuel Rico ; and Guillermo Gimé ; nez-Gallego
• 刊名：Biochemistry
• 出版年：2000
• 出版时间：May 2, 2000
• 年：2000
• 卷：39
• 期：17
• 页码：4982 - 4993
• 全文大小：690K
• 年卷期：v.39,no.17(May 2, 2000)
• ISSN：1520-4995

文摘

A shortened genetically engineered form of acidic fibroblast growth factor (aFGF), that includesamino acids 28-154 of the full-length sequence (154 residues) plus Met in substitution of Leu27, doesnot induce cell division even though it is recognized by the cell membrane receptor, triggers the earlymitogenic events, and retains the neuromodulatory, vasoactive, and cardio- and neuroprotective propertiesof the native full-length molecule. Taken together, these properties make this truncated aFGF a promisingcompound in the treatment of a wide assortment of neurological and cardiovascular pathologies whereaFGF mitogenic activity is dispensable. Differences in biological activities between the shortened aFGFand the wild-type form have been attributed to lack of stability, and to the specific amino acid sequencemissing at the N-terminus. Here we show that this shortened aFGF form has a three-dimensional structureeven more stable than the wild-type protein at the mitogenic assay conditions; that this structure is similarto that of the wild type except at site 1 of interaction with the cell membrane receptor; that its lack ofmitogenic activity cannot be attributed to the specific missing sequence; and that the vasodilatory activityof aFGF seems impaired by alterations of the three-dimensional structure of site 2 of interaction with thecell membrane receptor.