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Chloroplast Transit Peptides: Structure, Function and Evolution

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Chloroplast Transit Peptides: Structure, Function and Evolution reviews Chloroplast transit Although the first demonstration of precursor trans- port into chloroplasts was shown over two decades peptides: structure, ago3,4, only now is this area of cell biology becom- ing well understood. Many excellent reviews have been published recently on the evolution of plas- function and tids5, the evolution of organelle genomes6, the mechanism of gene transfer from organelles to the nucleus7 and the mechanism of protein import into evolution chloroplasts8,9. Proteins destined to plastids and other organ- elles share in common the requirement for ‘new’ Barry D. Bruce sequence information to facilitate their correct trafficking within the cell. Although in most cases this information resides in a cleavable, N-terminal sequence often collectively referred to as signal It is thought that two to three thousand different proteins are sequence, the different organelle-targeting se- targeted to the chloroplast, and the ‘transit peptides’ that act as quences have distinct properties and names: ‘signal peptides’ for the endoplasmic reticulum, chloroplast targeting sequences are probably the largest class of ‘presequences’ for the mitochondria and ‘transit peptides’ for chloroplasts and other plastids. This targeting sequences in plants. At a primary structural level, transit review focuses on recent progress in dissecting peptide sequences are highly divergent in length, composition and the role of the stromal-targeting domain of chloro- plast transit peptides. I will consider briefly the organization. An emerging concept suggests that transit peptides multitude of distinct functions that transit peptides contain multiple domains that provide either distinct or overlapping perform, provide an update on the limited struc- tural information of a number of transit peptides functions. These functions include direct interaction with envelope and finally give some ideas on their evolution. Figure 1 provides a schematic illustration of the lipids, chloroplast receptors and the stromal processing peptidase. chloroplast translocation apparatus and a work- The genomic organization of transit peptides suggests that these ing model of different transit peptide-mediated in- teractions that must occur during successful protein domains might have originated from distinct exons, which were import. This model is based on multiple obser- vations and contributions from several laboratories shuffled and streamlined throughout evolution to yield a modern, and has been simplified for the purposes of this multifunctional transit peptide. Although still poorly characterized, review. this evolutionary process could yield transit peptides with different The pool size of chloroplast precursors With the recent progress in genomic sequencing domain organizations. The plasticity of transit peptide design is efforts, it is not surprising that the number of po- consistent with the diverse biological functions of chloroplast proteins. tential chloroplast precursors identified is growing rapidly. Although certainly not up to date, the CHLPEP database10 contains sequences for nearly 300 different transit peptides. A similar database today might contain well over a thousand dif- Barry Bruce is in The family of plant organelles, collectively known ferent transit peptides. However, it is difficult to the Dept of as plastids, are widely accepted to have evolved know how many different precursors are targeted to Biochemistry, from free-living cyanobacteria through the process plastids during the life span of a typical plant. Cellular and of endosymbiosis. Although a modern plastid still Recently, ChloroP, a neural network-based method Molecular Biology retains a semi-autonomous genome, its coding of predicting transit peptides was used to analyse Department, The capacity has been reduced to only 100–200 genes. the 715 Arabidopsis proteins found in SWISS- Center for Legume The now classic assumption of the endosymbiotic PROT11. ChloroP showed that 13–22% of the pro- Research, theory, which was initially articulated by Weeden1, teins contained potential chloroplast transit pep- University of is that the proteins encoded by the genes newly tides. Extrapolating to the entire Arabidopsis Tennessee- transferred from the endosymbiant to the host gen- genome12,13, using even the lower value (13%), gives Knoxville, The ome will return to the organelle from which they a predicted number of chloroplast-targeted precur- Graduate Program originated. Considering that a typical cyanobacteria sors of 2900–3500, depending upon the estimated in Genome Science contains ~3200 genes2, several thousand gene prod- size of the genome. However, it is both interest- and Technology, ucts must be targeted back to the plastid to enable ing and reassuring that analysis of the existing University of the same level of metabolic complexity in a modern Arabidopsis genomic databases with the best com- Tennessee and Oak plant cell as existed in the ancestral cyanobacteria. putational tools currently available confirms the Ridge National The vast majority of these proteins are targeted back original predictions on the number of chloroplast Laboratory. into the chloroplast as a precursor protein whose precursors required to permit plastid metabolic E-mail: transport is facilitated by the acquisition of an N- complexity to approach that of a free-living cyano- [email protected] terminal extension referred to as a transit peptide. bacterium12,13. 440 0962-8924/00/$ – see front matter © 2000 Elsevier Science Ltd. All rights reserved. trends in CELL BIOLOGY (Vol. 10) October 2000 PII: S0962-8924(00)01833-X reviews Precursor *Precursor 1 2c 2a 2b Cytoplasm 346 5 + NTP? + GTP? OM 7 + ATP IMS IM + ATP 8 Stroma Contact site MGDG Toc86/159 Toc75 14-3-3 Toc34 Com70 IAP70 Phosphoserine PG/SL ClpC Tic40 Tic55 Tic110 CSS1 Tic20 Tic22 trends in Cell Biology FIGURE 1 General import pathway for plastid precursor import. Three hypothetical domains of the transit peptide are shown in red, green and yellow. Multiple steps of transit peptide-mediated protein import are shown by the following numbers: (1) Interaction of the precursor containing a phosphorylated serine in the transit peptide (*precursor) with soluble factors such as the molecular chaperone 14–3–3 protein in the cytoplasm. (2a) Partitioning of the precursor out of the cytoplasm on to the chloroplast surface through a direct NTP-independent interaction of the transit peptide with the chloroplast-specific lipids monogalactosyldiacylglycerol (MGDG), sulfolipid (SL) and phosphatidylglycerol (PG). (2b and 2c) Direct interaction of the precursor with Toc components, facilitated by association with the 14–3–3 molecular chaperone. (3) Peptide–lipid interactions resulting in reciprocal changes in both the transit peptide structure (shown as a green helix) and the lipid phase preference of the envelope (shown as an inverted micelle). (4) Recognition and interaction of transit peptide with Toc86/159 receptor. (5 and 6) Lateral movement and/or association of Toc86/159 with Toc34, resulting in the creation of a membrane contact site containing both the inner and outer envelope translocons. This also illustrates the sequential or concurrent GTP-driven insertion of the transit peptide into Toc75. (7) Precursor translocation across the outer envelope membrane by a push–pull mechanism using the ATP-dependent molecular motor(s) Com70 and/or IAP70. (8) Precursor translocation across the inner envelop membrane by a push–pull mechanism using the ATP-dependent molecular motor(s) IAP70 and/or CSS1. Structural analysis of transit peptides for the ability of TFE to preferentially stabilize pep- In contrast to the rapid progress in elucidating the tides in a helical conformation, it is clear that this primary structure of chloroplast transit peptides, only helix stabilization is not indiscriminate but does in- limited information is available concerning the struc- deed reflect the underlying structural preferences of ture of transit peptides. The lack of structural infor- a given peptide sequence19. mation is not only a result of limited investigation Attempts to refine the identity and placement of but also might reflect a fundamental property of transit peptide structural elements have used multi- transit peptides. Experimental results reveal that, in dimensional NMR on either synthetic or recombi- an aqueous environment, transit peptides are largely nant transit peptides. To date, the only two structures unstructured14–16, reinforcing an earlier proposal that reported are for the ferredoxin20 and Rubisco acti- they have evolved to maximize the potential to form vase16 transit peptide from the algae Chlamydomonas. a random coil17. Attempts to measure the structure of Figure 2 shows the lowest-energy structures for these transit peptides have utilized membrane-mimetic sol- transit peptides. Both of these structures were deter- vents such as TFE (2,2,2-trifluoroethanol) and aqueous mined in the presence of TFE and shown to contain buffers containing detergent micelles. Analysis of a helix and a random coil. However, the order of transit peptides in these solvents by circular dichro- these two motifs is reversed. Ferredoxin has an a- 14–16,18 ism spectrometry has demonstrated that transit helix at its N-terminus from position A2–V13, fol- peptides might contain significant a-helical struc- lowed by an unstructured C-terminal domain of ~19 ture(s); for example, in the transit peptide for prSSU amino acids. By contrast, the activase peptide ex- (SStp), both the
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