Febs Letters Volume 101, Number 1-2./Volume 102, Number 1-2. [antikvár]

Volume 108, number 2 FEBS LETTERS December 1979 PRINCIPAL FOLDING PATHWAY AND TOPOLOGY OF ALL-|3 PROTEINS 0. B. PTITSYN, A. V. FINKELSTEIN and P. FALK (BENDZKO)* Institute of Protein Research. USSR Academy of Sciences. 142292 Poustchino, Moscow Region, USSR Received 27 February 1979 1. Introduction The majority of proteins with mainly /3-sheet secondary structure (aIl-/3 proteins [1] or simply (3-proteins) have the structure of a double |3-sheet rolled into an open or closed cylinder [1]. The topology of the j3-sheet in these proteins usually includes the 'Greek key' [2] (see fig.l), and the topologies of all such proteins are surprisingly similar [5,6]. This suggests that these proteins have a common folding mechanism which determines the principal folding pathways for /3-proteins. Now we propose a folding mechanism for ^-proteins which is based on very simple and physically reasonable assumptions. According to this mechanism the folding pathway and the final protein topology depend only on the total number of /3-strands and on the localization of the initiating complex in the given protein chain. It reduces the number of possible topologies for /3-protein from 10^ or 10® (depending on the number of /3-strands) to only a few. Nevertheless the topologies of all known 'Greek key' ^-proteins can be obtained on these pathways. 2. Methods The kinetic [7] and thermodynamic [8,9] consideration of the /3-structure formation in unfolded protein chains leads to the conclusion [5,10,11] that the most stable ß-hairpins are often formed from long |3-strands, each including two, three or even more * Permanent address; Central Institute of Molecular Biology, GDR Academy of Sciences, Berlin-Buch, GDR ttK Superoxide dismutase 33 Azurin 5 6 80 raz 5 6 era B8 si ?7 2S\-B I Prealbumin 2 Immunoglobulin domains jj Serine proteoses (N-a C-domoins) 2 Concanovalin A 3 (N-domain) ® Concanavalin A 01 (C-domoin) nmfl 8 7 4 5 6 3 2 1 Plcstocyonin 8 7 1 5 6 3 I 2 6 5 2 3 4 1 7 8 ¦Fl^- 7 6 3 4 5 2 1 QiRl " 5 6 3 2 6 5 2 3 4 1 Fig.l. Schematic representation of;3-protein structures with the 'Greek key' topology [1-4]. Left: top view of the open or closed cylinder. Right: plane representation of the double /3-sheet ('topologies' [ 2 ]). Dots show hydrogen bonds between ;3-strands (hydrogen bonds in plastocyanin have not been reported). /3-Strands included in the 'Greek key' (four strands) or the 'double Greek key' (five strands) are underlined. ElsevierlNorth-Holland Biomedical Press 101