Common Evolutionary Origin for Coated Vesicles and Nuclear Pore Complexes Devos D, Dokudovskaya S, Alber F, Marti-Renom MA, Chait BT, Sali A, Rout MP UCSF.

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Presentation transcript:

Common Evolutionary Origin for Coated Vesicles and Nuclear Pore Complexes Devos D, Dokudovskaya S, Alber F, Marti-Renom MA, Chait BT, Sali A, Rout MP UCSF Rockefeller U., NY

Eukaryotic cell internal membrane systems, such as the Golgi apparatus and the endoplasmic reticulum (ER) vesicular transport systems communicate amongst these internal membranes and the plasma membrane by coated vesicles (CV) Nucleus, a membrane system contiguous with the ER

Nuclear Pore Complex

The Nup (y) 84/ (h) 107 Complex is a central component of the NPC Lutzmann et al. (02) EMBO j. The yNup84/vNup107 complex is a stable, conserved, and necessary building block of the NPC [Harel et al., 03; Walther et al., 03]

yNup84 complex proteins Sec13, Seh1: (297 & 349 aa) WD repeat  -propellers Nup84: 726 aa, mainly alpha Nup85: 744 aa, mainly alpha Nup120: 1037 aa, N - mainly beta – mainly alpha - C Nup133: 1157 aa, N - mainly beta – mainly alpha - C Nup145C: 712 aa, mainly alpha

Remote homology detection protocol Based on (Guenther et al., Cell 1997), confirmed in (Yamada et al., PNAS 2001). Domain? Multiple alignment Predicted Sec Str

Results Nup84Nup85Nup145C Nup120Nup133 (310 residues) (36 residues)

Results Nup84Nup85Nup145C Nup120Nup133 (310 residues) (36 residues)

Repeats 4 % of all proteins contain repeats (Marcotte et al., 99). Both  -propeller and  -solenoids are amongst the most common repeat motifs in the human genomes. Both repeats are specific to eukaryotes and are believed to have arisen in the immediate precursors of eukaryotes or during the early eukaryotes stages, followed by very early and rapid expansion and diversification of the families (Smith et al., 99). The most common function of the repeats is to mediate protein- protein interactions. Both repeats are well suited to organization of multiple simultaneous or consecutive protein-protein interactions/cooperative multivalent interactions. Both repeats have already been detected in the central actors of both nuclear transfer machines (karyopherin and Sec13) and coat vesicles (AP2 and clathrin).

Experimental evidences ySec13/vSec13R and ySeh1/vSec13RL are shared components of the NPC and the COPII and COPI complexes. Disruptions in numerous proteins associated with CV disrupt NPC function and assembly (Sakumoto et al., 1999, Ryan & Wente, 2002). In vertebrate cells, COPI components are needed to disassemble the NE via their interaction with an NPC protein.

Summary

Evolution