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Replacement of residue Leu68 by hydrophobic but smaller in the van der Waals radiusvaline residue does not change the overall fold of the protein. Under crystallizationconditions (0.18 M tri-sodium citrate, 0.1 M Tris-HCl pH=8.0, 30% PEG 400 and 0.1 Msodium acetate pH=4.6, 8% PEG 4000) it forms the domain swapped dimer, similar to thewild type protein (Figure 2a).Fig. 2. Assumed biological molecule of hCCL68V (a). Superposition of hCC wt (black) andhCC L68V (grey) (b).Superposition of both molecules do not reveal significant differences between the dimericstructure obtained for the reference wild type and the variant of hCC (rmsd=0.414). Closerexaminations of the surroundings of the substituted position 68 (Figure 2b) also shows thatthe distance between an -helix and the -sheet part is the same in the case of both dimers.Therefore, lowered stability of the hCC variant in the monomeric form cannot be attributedto changes in the secondary or tertiary structure of the studied protein. Increaseddimerization susceptibility of hCC L68V the most likely arises from the disruption of thenetwork of hydrophobic interactions surrounding the native leucine residue.AcknowledgmentsThis work was supported by a grant of Polish Ministry of Science and Higher Education No2739/B/H03/2010/38 and DS/8440-4-0172-0.References1. Grubb, A. Adv. Clin. Chem. 35, 63-99 (2000).2. Janowski, R., Kozak, M., Jankowska, E., Grzonka, Z., Grubb, A., Abrahamson, M., Jaskólski, M.Nat. Struct. Biol. 8, 316-320 (2001).3. Olafsson, I., Grubb, A. Amyloid Int. J. Exp. Clin. Invest. 7, 70-79 (2000).4. Gudmundsson, G., Hallgrimsson, J., Jonasson, T.A., Bjarnason, O. Brain 95, 387-404 (1972).5. Szymańska, A., Radulska, A., Czaplewska, P., Grubb, A., Grzonka, Z., Rodziewicz-Motowidło, S.Acta Biochim. Pol. 56, 455-463 (2009).6. Neu, H.C., Heppel, L.A. J. Biol Chem. 249, 3685-3692 (1965).283