Designation of sequences involved in the “coiled-coil” interdomainal connections in fibrinogen: Construction of an atomic scale model |
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Authors: | Russell F Doolittle Danielle M Goldbaum Larry R Doolittle |
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Institution: | The Department of Chemistry University of California, San Diego La Jolla, Calif. 92093, U.S.A. |
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Abstract: | Primary structure studies on human fibrinogen (α2β2γ2) have revealed certain unusual features which are compatible with the existence of a three-stranded set of supercoiled α-helices thought to be characteristic of the keratin family of fibrous proteins. In particular, each of the three non-identical chains has two characteristic braces of cysteines separated by 111 residues. The three chains are apparently bound together at these two junctures in unique six-cysteine rings. The amino acid sequences between these unusual cysteine pairs (themselves separated in all six cases by three residues) are helix-permissive over significant portions of their lengths. Moreover, the non-polar residues tend to vary rhythmically. To test the proposition that these sequences do indeed correspond to the “coiled-coils” long ago predicted on the basis of wide-angle X-ray diffraction studies, we constructed a detailed, atomic scale model of a part of this region. To this end, we fashioned three α-helical segments, each 29 residues long and corresponding to the designated sequences of the α, β and γ-chains, respectively. In each case we incorporated a pitch of approximately 200 Å. We were then able to fit the three helices together in the two possible combinations which yield a pseudo-3-fold axis. In either case all polar residues extend away from the parallel three-stranded rope, and almost all the non-polar side-chains are directed toward the interior. We also constructed a separate model showing how the six cysteines at each end of the proposed rod-like segment are best arranged. The co-ordinates from both models were collected and utilized in a computer-graphic Molecular Modeling System which can display features of the models selectively. Various projections were plotted automatically, some of which are reproduced here. |
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