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Recent advances in the understanding of membrane protein assembly and structure

  • Gunnar von Heijne (a1)
    • Published online: 01 November 1999

1. Introduction 286

2. Membrane protein assembly in E. coli 286

2.1. Role of the SRP 287

2.2. YidC – a translocon component devoted to membrane proteins? 287

2.3. The TAT pathway 288

2.4. ‘Spontaneous’ membrane protein insertion 288

3. Membrane protein assembly in the ER 289

3.1. How TM segments exit the translocon 289

3.2. Proteins with multiple topologies 290

3.3. Stop-transfer effector sequences 291

3.4. Non-hydrophobic TM segments? 291

3.5. ‘Frustrated’ topologies 291

3.6. N-tail translocation across the ER 292

4. Membrane protein assembly in mitochondria 292

4.1. The Oxa1p pathway 292

4.2. The TIM22/54 pathway 293

5. Evolution of membrane protein topology 293

5.1. RnfA/RnfE – two homologous proteins with opposite topologies 293

5.2. YrbG – duplicating an odd number of TMs 294

6. Genome-wide analysis of membrane proteins 295

6.1. Prediction methods 295

6.2. How many membrane proteins are there? 295

6.3. The positive-inside rule 296

6.4. Dominant classes of membrane proteins 296

7. The structure of transmembrane α-helices 296

7.1. What TM helices look like 297

7.2. The ‘helical hairpin’ 297

7.3. Prolines in TM helices 297

7.4. Charged residues in TM helices: the ‘snorkel’ effect 298

7.5. The ‘aromatic belt’ 298

8. Helix–helix packing in a membrane environment 298

8.1. Lessons learnt from glycophorin A 298

8.2. Genetic screens for helix–helix interactions 299

8.3. Statistical studies 299

8.4. Membrane protein folding 299

9. Recent 3D structures 300

9.1. KcsA – the first ion channel 300

9.2. MscL – sensing lateral pressure changes 300

9.3. The cytochrome bc 1 complex 300

9.4. Fumarate reductase 301

9.5. Bacteriorhodopsin – watching a membrane protein at work 301

10. Concluding remarks 301

11. Acknowledgements 302

12. References 302

For a variety of reasons – not the least biomedical importance – integral membrane proteins are now very much in focus in many areas of molecular biology, biochemistry, biophysics, and cell biology. Our understanding of the basic processes of membrane protein assembly, folding, and structure has grown significantly in recent times, both as a result of new methodological developments, more high-resolution structure data, and the possibility to analyze membrane proteins on a genome-wide scale.

So what is new in the membrane protein field? Various aspects of membrane protein assembly and structure have been reviewed over the past few years (Cowan & Rosenbusch, 1994; Hegde & Lingappa, 1997; Lanyi, 1997; von Heijne, 1997; Bernstein, 1998); here, I will try to bring together a number of exciting recent developments. Particularly noteworthy are the discoveries related to the mechanisms of membrane protein assembly into the inner membrane of E. coli, the inner membrane of mitochondria, and the way transmembrane segments are handled by the ER translocon.

Other advances include detailed studies of the interaction between transmembrane helices and the lipid bilayer, and of helix–helix packing interactions in the membrane environment. The availability of full genomic sequences have made it possible to study membrane proteins on a genome-wide scale. Finally, a handful of new high-resolution 3D structures have appeared.

This review will deal only with helix bundle proteins, i.e. integral membrane proteins where the transmembrane segments form α-helices. For reviews on the other major class of integral membrane proteins – the β-barrel proteins – see Schirmer (1998) and Buchanan (1999). For readers who prefer a more ‘literary’ introduction to the membrane protein field, may I suggest von Heijne (1999).

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Quarterly Reviews of Biophysics
  • ISSN: 0033-5835
  • EISSN: 1469-8994
  • URL: /core/journals/quarterly-reviews-of-biophysics
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