التفاصيل البيبلوغرافية
| العنوان: |
Inhibition of Protein 4.1 R and NuMA Interaction by Mutagenization of Their Binding-Sites Abrogates Nuclear Localization of 4.1 R. |
| المؤلفون: |
Mattagajasingh, Subhendra N., Huang, Shu-Ching, Benz Jr., Edward J. |
| المصدر: |
CTS: Clinical & Translational Science; Apr2009, Vol. 2 Issue 2, p102-111, 10p, 2 Color Photographs, 1 Black and White Photograph, 5 Diagrams |
| مصطلحات موضوعية: |
PROTEINS, CELL proliferation, SPINDLE apparatus, DYNEIN, MUTAGENESIS, INTRACELLULAR pathogens, AMINO acids, CYTOSKELETAL proteins, TERATOGENESIS |
| مستخلص: |
Protein 4.1R(4.1R) is a multifunctional structural protein recently implicated in nuclear assembly and cell division. We earlier demonstrated that 4.1R forms a multiprotein complex with mitotic spindle and spindle pole organizing proteins, such as NuMA, dynein, and dynactin, by binding to residues 1788–1810 of NuMA through amino acids encoded by exons 20 and 21 in 24 kD domain. Employing random-and site-directed mutagenesis combined with glycine- and alanine-scanning, we have identified amino acids of 4.1 R and NuMA that sustain their interaction, and have analyzed the effect of mutating the binding sites on their intracellular colocalization. We found that V762, V765, and V767 of 4.1 R, and 11800, 11801,11803, Tl 804, and M1805 of NuMA are necessary for their interaction. GST-fusion peptides of the 4.1R24 kD domain bound to residues 1785–2115 of NuMA in in vitro binding assays, but the binding was inhibited by alanine substitutions of V762, V765, and V767 of 4.1 R, or residues 1800–1805 of NuMA. Additionally, expression of variants of 4.1 R or NuMA that inhibit their in vitro binding also abrogated nuclear localization of 4.1 Rand colocalization with NuMA. Our findings suggest a crucial role of 4.1 R/NuMA interaction in localization and function of 4.1 R in the nucleus. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
