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College Park, Maryland      June 6 - 10 , 2004

TP46: Characterization of Cryptophycin- and Dolastatin-Induced Tubulin Rings

H. Boukari (National Institutes of Health, Bethesda, Maryland, USA), S. Krueger (National Institute of Standards and Technology), R. Nossal, D. L. Sackett (National Institutes of Health, Bethesda, Maryland, USA)

We have applied small-angle neutron scattering (SANS) and dynamic light scattering (DLS) to probe interactions of the protein, αβ-tubulin, with either cryptophycin 1 or dolastatin 10, two small peptides extracted from marine products. These two peptides inhibit the polymerization of tubulin into microtubules and, instead, induce the formation of tubulin rings of about 24 and 44 nm diameter, respectively [1]. Under the studied conditions, the SANS and DLS measurements on cryptophycin-tubulin samples indicate a narrow structural dispersity with a predominant structure made of 8 tubulin dimers assembled into non-interacting rings. In contrast, dolastatin-tubulin samples show additional aggregation of the primary rings, composed mostly of 14 dimers, resulting in large structures that settle to the bottom of their container under the effect of gravity. Further modeling of the SANS profiles indicate, remarkably, that the dolastatin-tubulin aggregates are ordered structures, most likely columns of rings [2]. These rings can be used as potential models for investigating the behavior of closed ring polymers, which may intrinsically differ from open-ended linear biological polymers such as microtubules and actin filaments.

[1] H. Boukari, R. Nossal, D. L. Sackett, Biochemistry 42, 1292 (2003).
[2] H. Boukari, V. Chernomordik, S. Krueger, R. Nossal, and D. L. Sackett, Physica B (in press).

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