This volume of The Enzymes features high-caliber thematic articles on the topic of molecular machines involved in protein transport across cellular membranes. The book consists of five parts which span the range of membranes including bacterial, endoplasmic reticulum, mitochondrial, chloroplast, and peroxismal.
Cover 1
Contents 6
Preface 14
Part I: Crossing Bacterial Membranes 16
Chapter 1: Cotranslational Protein Targeting in Escherichia coli 1
I. Introduction 18
II. The Ribosome 19
A. The Ribosomal Tunnel 19
B. Sensing Nascent Secretory and Membrane Proteins in the Tunnel? 21
C. L23 at the Exit Site 23
III. Chaperones and Targeting Factors at the Ribosomal Tunnel Exit 23
A. SRP-Ribosome Interaction 23
B. TF-Ribosome Interaction 24
C. Interplay Between TF and SRP on the Ribosome 26
D. The Nascent Polypeptide-Associated Complex 28
E. The Hsp70-RAC Triad 29
IV. SRP-Mediated Targeting 29
A. General Features of SRP 31
B. Signal Peptide Binding to the M-Domain 32
C. The SRP Receptor FtsY 32
D. Inter- and Intramolecular Communication Between the SRP Components 33
V. Selection of Protein for SRP-Mediated Targeting 34
A. SRP-Mediated Targeting in E. coli Occurs Cotranslationally 36
B. How Important Is SRP for Bacteria? 37
VI. Concluding Remarks 38
Acknowledgments 39
References 39
Chapter 2: Sec Protein-Conducting Channel and SecA 50
II. Introduction 50
III. Outline 52
IV. Variation and Evolution of the Sec Machinery 52
A. The Canonical Bacterial Sec Machinery 52
B. Evolutionary History of the E. coli Sec Machinery 53
C. Sec Paralogues 55
V. SecA Structure, Function, and Dynamics 56
A. The Involvement of SecA in Cotranslational Protein Translocation 56
B. The Overall Mechanism of Posttranslational Protein Translocation 57
C. Structure of the SecA Protomer 58
D. Structure of the Functional SecA Dimer 63
E. Conformational Changes Within SecA 64
F. SecA-SecB Interaction 65
G. SecA-Membrane Interaction 66
VI. SecYEG Structure, Function, and Dynamics 66
A. Structure of the SecYEG Protomer 66
B. Arrangement of SecYEG Protomers Within an Oligomeric Assembly 71
C. Induction of Conformational Changes in SecYEG 73
D. The Role of the Plug 74
VII. Concluding Remarks 74
References 74
Chapter 3: Targeting of Proteins by the Twin-Arginine Translocation System in Bacteria and Chloroplasts 84
I. Introduction 84
II. Basic Features of Tat Systems, Their Discovery, and Their Distribution 85
III. tat Genes and Mutant Phenotypes 86
A. tat Genes in Gram-Negative Bacteria 86
B. tat Mutant Phenotypes and Substrate Specificities in Gram-Negative Bacteria 87
C. tat Genes in Plants 91
D. tat Genes in Gram-Positive Organisms and Archaea 92
IV. The Tat Subunits: Structures and Conserved Regions 93
V. Structures of Tat Complexes 95
VI. Tat Signal Peptides 97
VII. The Tat Mechanism 99
A. The Translocation Mechanism Used by the E.coli and Thylakoid Tat Systems 99
B. A Different Translocation Mechanism in B. subtilis? 100
References 102
Chapter 4: YidC: A Protein with Multiple Functions in Bacterial Membrane Biogenesis 108
I. Introduction 108
II. The YidC Pathway 111
III. Sec-YidC Pathway 112
IV. YidC Substrates 114
V. YidC Family of Proteins 115
VI. Concluding Remarks and Outlook 120
References 1
Chapter 5: Disulfide Bond Formation Enzymes 126
I. Disulfides Stabilize Secreted Proteins 126
II. The Need for a Catalyst 127
III. DsbA: The Primary Oxidant 127
IV. Structure of DsbA 131
V. How Is DsbA Reoxidized? 132
VI. Reoxidation of DsbB 134
VII. Disulfide Bond Isomerization 136
VIII. DsbD a Disulfide Transporter? 138
References 1
Chapter 6: The Identification of the YaeT Complex and Its Role in the Assembly of Bacterial Outer Membrane beta-Barrel Proteins 144
II. Gram-Negative Bacterial Envelope 145
III. Protein Transport Across the Bacterial Envelope 145
IV. Identification of OM Biogenesis Factors: The Search for Needles in a Haystack 150
V. Chemical Conditionality: The YfgL Connection to OM Assembly 151
VI. Identification and Characterization of the YaeT Complex 153
VII. Interactions Among YaeT Complex Members 156
VIII. POTRA Domains 157
IX. Properties of the YaeT-Like beta-Barrel Domains 159
X. Conclusions and Future Study 160
References 1
Chapter 7: The Function of the ABC Transporter LolCDE in Protein Transport to the Outer Membrane of E. coli 166
II. Introduction 167
A. Structure and Function of Outer Membrane Proteins in Gram-Negative Bacteria 167
B. Biogenesis of Lipoproteins 169
C. Lipoprotein-Sorting Signals 171
III. Sorting of Lipoproteins by the Lol System 172
A. Localization of Lipoproteins 172
B. LolA, a Periplasmic Chaperon for Lipoproteins 172
C. LolB, an Outer Membrane Receptor for Lipoproteins 173
D. Structures of LolA and LolB 174
E. LolCDE, an ABC Transporter Mediating the Membrane Detachment of Lipoproteins 175
F. Perspectives 184
Acknowledgments 185
References 185
Part II: Crossing Endoplasmic Reticulum Membranes 190
Chapter 8: The Signal Recognition Particle and Its Receptor in ER Protein Targeting 192
II. Introduction 193
III. Cotranslational Translocation: A Historical Perspective 195
A. The Signal Hypothesis 196
B. mRNA Partitioning 198
IV. Targeting of Proteins to the ER Is Regulated by Unusual GTPases 201
A. Characterization of the SRbeta Subunit of the SR 202
B. Docking the Ribosome on the Translocon 205
V. Structure-Function Analysis 206
A. Signal Recognition Particle 206
B. SRP RNA 207
C. SRP9 and SRP14 209
D. SRP68 and SRP72 210
E. SRP19 211
F. SRP54 211
G. SRP21, an SRP Subunit Unique to Yeast 214
H. Engaging the Translocation Complex 214
VI. Conclusions 215
Acknowledgments 215
References 1
Chapter 9: The Translocation Apparatus of the Endoplasmic Reticulum 222
II. Translocons Receive Substrates via Two Distinct Pathways 223
III. Substrate Recognition by the ER Translocon Is a Decisive Step in Protein Translocation 224
IV. The Remarkable Diversity of Sequences Recognized by the Translocon 228
V. The Machinery of Signal Sequence Recognition 229
VI. A Combined Framework for Signal and TMD Recognition 231
VII. Gating of the Protein-Conducting Channel of the Translocon 234
VIII. The Energetics of Protein Translocation 238
IX. The Biogenesis of Membrane Proteins 240
X. Lateral Exit of TMDs from the Translocon 243
XI. Regulation of Protein Translocation 246
References 1
Chapter 10: The Role of BiP/Kar2p in the Translocation of Proteins Across the ER Membrane 1
II. Hsp70 1
A. The Structure of Hsp70 1
B. The Hsp70 Reaction Cycle 263
C. BiP/Kar2p 264
III. Protein Translocation into the ER 265
A. The Sec Complex 266
B. Posttranslational Translocation 269
C. Cotranslational Translocation 271
IV. Folding of Nascent Proteins in the ER and ER-Associated Degradation (ERAD) 274
V. Unanswered Questions 276
Acknowledgments 277
References 277
Chapter 11: Calnexin, Calreticulin, and Their Associated Oxidoreductase ERp57 1
II. Introduction 1
III. Structural Characteristics of Calnexin and Calreticulin 1
A. Carbohydrate-Binding Site 1
B. P-Domain 295
C. Retention Signals 296
D. Regulatory Domains 296
IV. The Roles of Calnexin and Calreticulin in Glycoprotein Maturation and Quality Control 1
A. Topological Constraints Control Lectin Chaperone Functions 298
B. Lectin Chaperones Involvement in Quality Control 300
C. Peptide-Binding Function 301
V. The Calnexin-Binding Cycle in Yeast 303
VI. ERp57, a Member of the PDI Family of Oxidoreductases 304
A. Structural Insights into ERp57 from the PDI Crystal Structure 304
B. ERp57 Docking onto Its Partner Lectin Chaperones 307
VII. Redox Activity of ERp57 307
VIII. The Role of ERp57 in Glycoprotein Folding 309
IX. Regulation of Calcium Signaling 311
X. Summary 312
References 313
Part III: Crossing Mitochondrial Membranes 322
Chapter 12: TOM and SAM Machineries in Mitochondrial Protein Import and Outer Membrane Biogenesis 324
II. Introduction 325
A. Structural Features of Mitochondrial Proteins 326
III. The TOM Complex 328
A. The Core TOM Complex: A Primitive Protein Translocase? 328
B. The Holo-TOM Complex: The Addition of Recently Evolved TOM Receptor Proteins 336
IV. The SAM Complex 341
A. Machinery for the Assembly of Complex Proteins into the Mitochondrial Outer Membrane 341
B. Additional Modules of the SAM in the Outer Membrane 345
V. Concluding Remarks 347
Acknowledgments 348
References 348
Chapter 13: The Role of the Mia40-Erv1 Disulfide Relay System in Import and Folding of Proteins of the Intermembrane Space of Mitochondria 360
II. Introduction 361
III. Protein Import Routes into the IMS 362
IV. Mia40, an Import Receptor in the IMS 364
A. Structural Organization of Mia40 Proteins 364
B. The Function of Mia40 in the IMS 365
V. Erv1, a Disulfide Oxidase in the IMS 366
A. Structural Organization of Erv1 Proteins 366
B. Other Proteins with Erv1-Like Domains 368
C. Functions of Erv1 in the IMS 370
VI. A Model of Mia40-Erv1-Mediated Import 372
VII. Substrate Proteins of the Mia40-Erv1 Pathway 375
A. Proteins of the Twin Cx3C Family 375
B. Proteins of the Twin Cx9C Family 375
VIII. Perspectives 376
Acknowledgments 377
References 377
Chapter 14: The Function of TIM22 in the Insertion of Inner Membrane Proteins in Mitochondria 382
II. Introduction 383
III. Properties of Precursors that Utilize the TIM22 Import Pathway 385
IV. The Small Tim Proteins 388
V. The TIM22 Inner Membrane Complex 390
VI. Disease Connections 392
References 394
Chapter 15: The Role of the TIM23 Complex and Its Associated Motor Complex in Mitochondrial Protein Import 402
II. Introduction 403
III. Mitochondrial Presequence Proteins 405
A. The Structure of the Presequence 406
B. Functions of the Presequence 406
C. Processing and Sorting of the Mature Protein 407
IV. The Presequence Translocase: TIM23 Complex 407
A. Components of the TIM23 Complex 408
B. The Tim23 Channel and Its Regulation 409
V. Energy Requirement for Matrix Translocation: The Motor Complex 410
A. The Membrane Potential and ATP-Hydroplysis Drive Protein Import 410
B. MtHsp70: The Central Component of the Motor Complex 410
C. Components of the Motor Complex 411
VI. Models of Motor Function 413
A. Protein Unfolding for Import 413
B. Two Models of Hsp70 Function for Matrix Import 413
C. Functional Implication of PAM Organization for Hsp70 Regulation 414
VII. Transport of Proteins Across Two Membranes 415
A. Structural Connection Between Translocases on the Outer and Inner Membrane 415
B. The .TOM-TIM.23 Supercomplex 416
VIII. Protein Transport Through Two Different Forms of the Presequence Translocase 417
Acknowledgments 418
References 418
Part IV: Crossing Chloroplast Membranes 428
Chapter 16: The Toc Machinery of the Protein Import Apparatus of Chloroplasts 430
I. Introduction 430
II. General Overview of Toc Complexes 432
III. Toc Receptors 433
IV. The Toc Translocon Channel and Membrane Translocation 438
V. Cytoplasmic Events 440
VI. Toc Complex Evolution and Diversity 441
VII. Toc Complex Assembly 445
VIII. Future Directions 447
References 448
Chapter 17: The Role of the Tic Machinery in Chloroplast Protein Import 454
II. Introduction 455
III. Tic110: The Translocation Channel 456
IV. Tic40: The Cochaperone 461
V. Tic20: A Putative Channel Protein 464
VI. Tic22: A Connection to Toc in the Intermembrane Space 466
VII. Tic32: A Short Chain Dehydrogenase 467
VIII. Tic62: The FNR-Binding Protein 468
IX. Tic55: The Rieske-Family Member 469
X. Traveling Back in Time 470
References 1
Chapter 18: The Sec and Tat Protein Translocation Pathways in Chloroplasts 478
II. Overview of Protein Trafficking to the Plant Thylakoid Membrane and Lumen 479
III. Targeting to the Sec and Tat Pathways 481
IV. The Sec Transport System in Chloroplasts 483
A. Introduction 483
B. Thylakoid Components 484
C. Capabilities and Operation of the Thylakoid Sec System 484
D. cpSecY2 and cpSecA2 486
E. Prospects 487
V. The Tat System in Chloroplasts 487
A. Introduction 487
B. Capabilities and Requirements of the Thylakoid Tat System 488
C. Operation of the Tat System 494
D. Models for the Tat Translocase and Future Directions 499
Acknowledgments 501
References 1
Chapter 19: Chloroplast SRP/FtsY and Alb3 in Protein Integration into the Thylakoid Membrane 508
II. Introduction 509
III. The General Pathway for Posttranslational Targeting of LHCPs by cpSRP 510
IV. Soluble and Membrane Components of the Posttranslational SRP Pathway 512
A. cpSRP Is Composed of a Conserved 54-kDa GTPase and a 43-kDa Subunit Unique to Chloroplasts 512
B. A cpSRP Receptor Homologue Is Required for cpSRP-Based Protein Targeting to the Thylakoid Membrane 514
C. LHCP Integration Appears Independent of Thylakoid Sec and TAT Transport Pathways 515
D. The Oxa1/Alb3/YidC Family Functions in LHCP Integration 515
E. Posttranslational Binding to cpSRP is Linked to an Alb3 Requirement for Integration 517
V. Steps in the Posttranslational SRP Targeting Pathway 517
A. cpSRP Assembly 517
B. Transit Complex Formation 519
C. Membrane Events in the Posttranslational cpSRP Pathway 522
VI. An Overlapping Post- and Cotranslational Function of cpSRP/cpFtsY/Alb3 524
A. Biochemical Evidence for a Cotranslational cpSRP-Targeting Pathway 524
B. Analysis of Mutants Lacking Components of the cpSRP Pathway 525
VII. Conclusions and Outlook 530
Note Added In Proof 531
Acknowledgments 531
References 531
Part V: Crossing Peroxisomal Membranes 538
Chapter 20: The Role of Shuttling Targeting Signal Receptors and Heat-Shock Proteins in Peroxisomal Matrix Protein Import 540
I. Catalytic Machines Involved in Peroxisomal Matrix Protein Import 540
II. Components Involved in Peroxisomal Matrix Protein Import 541
A. Receptor Shuttling During Peroxisomal Matrix Protein Import 543
B. The Peroxisomal RADAR Pathway 545
C. PTS Receptor-Mediated Steps in the Matrix Protein Import Cycle 546
D. Energetics of Receptor Recycling and Cargo Import 548
III. Role of Hsp70 Family of Proteins in Peroxisomal Matrix Protein Import 549
Acknowledgments 551
References 551
Chapter 21: Function of the Ubiquitin-Conjugating Enzyme Pex4p and the AAA Peroxin Complex Pex1p/Pex6p in Peroxisomal Matrix Protein Transport 556
I. Introduction 556
II. Peroxisomal Matrix Protein Import 557
A. Import of Folded and Oligomeric Proteins Across the Peroxisomal Membrane 558
B. Sequential Model for PTS-Receptor Cycle 558
III. Overview: Enzymes Involved in Ubiquitination 561
A. Enzymatic Cascade for Protein Modification 561
B. Downstream Components of Ubiquitin-Based Protein-Targeting Systems 562
IV. The Ubiquitin-Conjugating Enzyme Pex4p in Peroxisome Biogenesis 563
A. Ubiquitin-Conjugating Enzymes of the Ubc4p Family Involved in PTS Receptor Regulation 563
B. Function of Pex4p/Ubc10p in Receptor Recycling 566
C. Peroxisomal RING-Finger Proteins as Putative Ubiquitin-Ligase-Complex 568
V. The AAA Family ATPases 570
A. Function and Structure of AAA-Type ATPases 570
B. AAA ATPases in Protein Transport 571
VI. Pex1p and Pex6p: AAA Proteins Required for Peroxisomal Biogenesis 572
A. ATP-Dependency of Matrix Protein Import 572
B. Structural Characterization of the AAA Peroxins 573
C. Similarities of the Peroxisomal Import Machinery with ERAD Components 573
VII. Receptor Ubiquitination: A Link Between Pex4p, AAA Peroxins, and Protein Transport? 576
References 579
Author Index 588
Index 638
Cotranslational Protein Targeting in Escherichia coli
Ronald S. Ullersa; Pierre Genevauxb; Joen Luirinkc a Department of Microbiology and Molecular Medicine, Centre Médical Universitaire, CH-1211 Geneva, Switzerland
b Laboratoire de Microbiologie et Génétique Moléculaires, IBCG, CNRS, Université Paul-Sabatier, 118, route de Narbonne, 31062 Toulouse cedex 09, France
c Department of Molecular Microbiology, Institute of Molecular Cell Biology, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands
Publisher Summary
The genetic and biochemical data concerning the signal recognition particle (SRP)-targeting pathway in E.coli, together with the recently available structures of most of the players in the field, have significantly expanded the knowledge of the functions of these players and of the interplay among these protein complexes. This chapter focuses on the different stages of SRP-mediated protein targeting in bacteria—from the synthesis on ribosome to the final handover of the protein to the SecYEGcomplex in the inner membrane (IM)—and on the complexity of interactions between the newly synthesized polypeptides and cellular factors that control their destiny. In E. coli, SRP binds to the large ribosomal subunit component L23, where it interacts with hydrophobic transmembrane TM segments in nascent inner membrane proteins (IMPs) emerging from the ribosome. However, several pressing issues need to be addressed such as additional structural investigations of the interactions among modules of the same species that are crucial and need to be carried out. However, more structural data are required that will undoubtedly shed light on the fascinating relationship between chaperones and targeting factors during the early events of protein targeting to the E. coli IM.
I Introduction
In all organisms, genetic messages are translated primarily by cytosolic ribosomes, yet the translation products end up in a variety of cellular locations. Nascent polypeptide chains emerging from the ribosomal exit are facing a pool of chaperones, folding catalysts, and targeting factors, which efficiently partition between proteins that need to be folded in the cytosol and proteins that need to be transferred into or through membranes. In Gram-negative bacteria, proteins destined for the secretory apparatus are equipped with an N-terminal extension called the signal peptide (reviewed in [1]). The signal peptide directs the secretory proteins (periplasmic and outer membrane proteins) into the SecB pathway, where, during or after translocation through the inner membrane (IM), the signal peptides are cleaved off by signal peptidases. Most inner membrane proteins (IMPs) lack a cleavable signal peptide. They are anchored into the IM by hydrophobic α-helical transmembrane (TM) segments. These TM segments may also act as targeting signals in which case they are recognized by the signal recognition particle (SRP) that directs the polypeptides to the Sec complex at the IM (reviewed in [2, 3]). In contrast to translocation of unfolded proteins across the IM via the Sec system, the twin-arginine translocation (TAT) system can only transport proteins that are completely folded (reviewed in [4]).
The decision on a protein's destiny is probably made early during its synthesis on the ribosome, since both SRP and chaperones such as trigger factor (TF) bind close to the ribosomal exit site where they can associate with the emerging nascent chain. In this chapter, we will focus on the different stages of SRP-mediated protein targeting in bacteria—from the synthesis on the ribosome to the final handover of the protein to the SecYEG complex in the IM—and on the complexity of interactions between the newly synthesized polypeptides and cellular factors that control their destiny.
II The Ribosome
Protein synthesis is catalyzed by the ribosome, a highly conserved macromolecular complex present in all living cells [5]. Both the small and large subunit of the ribosome is composed of RNA and proteins. The small subunit mainly decodes genetic information [6, 7], while the large subunit is responsible for peptide elongation and protein release. Peptide bond formation occurs in the peptidyl transferase center (PTC) [8, 9].
A THE RIBOSOMAL TUNNEL
Crystal structures of archaeal and eubacterial large ribosomal subunits [8–12] show a long tunnel running from the PTC to the ribosomal proteins L23/L24/L29 at the surface of the ribosome. It has been suggested that this is the normal exit path from the ribosome for nascent peptides [10]. However, some polypeptides may leave the PTC via the interface of the two ribosomal subunits [13]. In addition, three-dimensional cryo-electron microscopy (EM) maps of the ribosome reveal several side branches of the tunnel that may reflect alternative exit sites [14, 15]. Nevertheless, cross-linking studies suggest that nascent chains, irrespective of their future destination, exit the ribosome near L23 [16–19].
The length of the main tunnel is about 100 Å, and its diameter varies from 10 to 20 Å. The inner surface of the tunnel consists mainly of rRNA, but nonglobular parts of the ribosomal proteins L4 and L22 also contribute [9, 10]. The resulting surface is largely hydrophilic and uncharged, thus facilitating the passage of all kinds of peptide sequences [10]. A long β-hairpin loop of L22 lies approximately parallel to the tunnel axis, making this ribosomal protein the largest protein contributor to the inner surface of the tunnel. The ribosomal proteins L23, L24, and L29 flank the exit of the tunnel.
The tunnel was initially thought to be a narrow passage through a rigid structure that precludes significant protein folding [10]. Structural studies, however, suggest that the ribosome is rather dynamic and adopts different functional conformations [15,20–22]. In addition, several reports have demonstrated that nascent proteins fold to various degrees inside the ribosome [23–26]. Consequently, the ribosomal tunnel must expand considerably during protein synthesis to accommodate folded nascent polypeptides [24, 27]. However, this view has been questioned by Voss et al. [28]. On the basis of geometric analysis of the ribosomal tunnel in Haloarcula marismortui, it was proposed that the tunnel is not wide enough to accommodate folded polypeptides larger than α-helices [28].
Although the ribosomal tunnel wall has a “nonstick” character [10], certain nascent chains can interact with the tunnel, thereby causing translational pausing (reviewed in [13, 29, 30]). One striking example is the SecM protein [31]. SecM includes a 17 amino acid sequence motif that can block protein elongation and create a stalled ribosomal complex in the absence of a functional protein export system. It was demonstrated by fluorescence resonance energy transfer (FRET) that the SecM C-terminus adopts a compact conformation on synthesis of the arrest motif, which appeared essential for the translocation arrest and which was specifically induced by the ribosome [26]. It was proposed that translation arrest by SecM results from series of reciprocal interactions between the ribosome and the C-terminal part of the nascent SecM polypeptide. On the basis of cryo-EM reconstructions of pretranslocational and SecM-stalled Escherichia coli ribosome complexes, Mitra et al. [32] also suggested that SecM induces a cascade of ribosomal conformational changes that lock the mRNA-tRNA complex on the ribosome, such that elongation is stalled [32]. It was previously shown that SecM-mediated elongation arrest can be bypassed by mutations in the 23S rRNA or in L22 at a constriction area in the tunnel, which might act as a discriminating gate [31]. Taken together, the cryo-EM and the biochemical data suggest that nascent chain interactions and structural rearrangements in the ribosomal interior affect translation rates of nascent polypeptide chains.
B SENSING NASCENT SECRETORY AND MEMBRANE PROTEINS IN THE TUNNEL?
As discussed above, nascent peptides may have specific interactions already in the ribosome tunnel, which may regulate translation. In addition, specific interactions and conformational changes in the ribosome may be sensed and transduced to the surface of the ribosome influencing downstream interactions and topogenesis of the protein synthesized [13, 29, 30]. In concreto, future TM segments may be recognized already inside the ribosome. These intraribosomal contacts may have a profound impact on downstream processes such as the extraribosomal contacts with chaperones, targeting factors, and translocon components (reviewed in [33]). A fluorescence quenching study from the Johnson group has indicated that, in eukaryotes, a TM segment inside the ribosome induces conformational changes in the Sec translocon in the endoplasmic reticulum (ER) membrane [34]. How is the presence of a TM segment at the entrance of the ribosomal tunnel signaled to the exit site of the ribosome, and sequentially, causes a conformational change in the translocon?
This question has been...
| Erscheint lt. Verlag | 28.8.2007 |
|---|---|
| Sprache | englisch |
| Themenwelt | Naturwissenschaften ► Biologie ► Biochemie |
| Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie | |
| Naturwissenschaften ► Biologie ► Zellbiologie | |
| Naturwissenschaften ► Physik / Astronomie ► Angewandte Physik | |
| Technik | |
| ISBN-10 | 0-08-055216-1 / 0080552161 |
| ISBN-13 | 978-0-08-055216-3 / 9780080552163 |
| Haben Sie eine Frage zum Produkt? |
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