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The biological function of a fragment of the neurotrophic factor from pigment epithelium: Structural and functional homology with the differentiation factor of the HL-60 cell line
Authors:I. A. Kostanyan  S. S. Zhokhov  M. V. Astapova  S. M. Dranitsyna  A. P. Bogachuk  L. K. Baidakova  I. L. Rodionov  I. I. Baskin  O. N. Golubeva  J. Tombran-Tink  V. M. Lipkin
Affiliation:(1) Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117871 GSP-7 Moscow, Russia;(2) Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, 142290 Pushchino, Moscow oblast, Russia;(3) Chemical Faculty, Moscow State University, Vorob’evy Gory, 119899 Moscow, Russia;(4) Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia;(5) Center for Neuroscience Research, Children’s National Medical Center, George Washington University, Washington, DC, USA
Abstract:It was shown that the full-size neurotrophic factor from pigment epithelium (PEDF) induces the cell differentiation of the human promyelocyte leukemia cell line HL-60. A structural analysis of PEDF revealed in itsC-terminal region a six-membered peptide fragment PEDF-(352-357) (PEDF-6) whose sequence is highly homologous to the 41–46 fragment of the active site of the human leukocyte differentiation factor HLDF (HLDF-6). The biological effect of PEDF and synthetic peptides PEDF-6 and HLDF-6 on the HL-60 cells and the early gastrula ectoderm ofXenopus laevis embryos was studied. On the basis of the structural and functional homologies of HLDF, PEDF, and their homologous peptides and the computer models of the spatial structures of the full-size PEDF and the PEDF with theC-terminal fragment split off tby the cleavage of the Leu380-Thr381 bond in the serpin loop, a hypothesis on the functional role of the serpin loop in PEDF was put forward.
Keywords:cell differentiation  cell differentiation factors  peptides, computer modeling
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