Review Article
A superfamily of small potassium channel subunits: form and function of the MinK-related peptides (MiRPs)
- GEOFFREY W. ABBOTT, STEVE A. N. GOLDSTEIN
-
- Published online by Cambridge University Press:
- 01 November 1998, pp. 357-398
-
- Article
- Export citation
-
1. INTRODUCTION 358
1.1 Summary 358
1.2 Overview 359
1.3 Four classes of pore-forming K+channel subunits – necessary and (sometimes) sufficient 361
1.4 Soluble and peripheral membrane proteins that interact with P loop subunits to alter function 362
1.5 Integral membrane proteins that interact with P loop subunits to alter function 363
2. MinK DETERMINES THE FUNCTION OF MIXED CHANNEL COMPLEXES 363
2.1 The KCNE1 gene product (MinK) gives rise to K+-selective currents and controversy 363
2.2 MinK assembles with a P loop protein, KvLQT1, to form K+channels with unique function 364
2.2.1 Single-channel conductance of KvLQT1 and MinK/KvLQT1 channels 366
2.2.2 Other differences between KvLQT1 and MinK/KvLQT1 channels 367
2.3 MinK assembles with HERG, another P loop subunit, to regulate channel activity 368
2.4 MinK does not form chloride-selective ion channels 368
3. EXPERIMENTAL AND NATURAL MinK MUTATIONS 369
3.1 Site-directed mutations 369
3.1.1 MinK mutation alters basic channel attributes and identifies key residues 369
3.1.2 MinK is a Type I transmembrane peptide 370
3.1.3 MinK is intimately associated with the IKspore 370
3.1.4 The number of MinK subunits in IKschannel complexes 372
3.2 KCNE1 mutations associated with arrhythmia and deafness alter IKschannel function 373
3.3 Summary of MinK sites critical to IKschannel function 374
4. MinK-RELATED PEPTIDES: AN EMERGING SUPERFAMILY 374
4.1 KCNE2, 3 and 4 encode MinK-related peptides 1, 2 and 3 (MiRPs) 374
4.2 MiRP1 assembles with a P loop protein, HERG, to form K+channels with unique function 375
4.2.1 MiRP1 alters activation, deactivation and single-channel conductance 376
4.2.2 MiRP1 alters regulation by K+ion and confers biphasic kinetics to channel blockade 378
4.2.3 Stable association of MiRP1 and HERG subunits 380
4.3 KCNE2 mutations are associated with arrhythmia and decreased K+flux 383
4.4 Summary of the evidence that cardiac IKrchannels are MiRP1/HERG complexes 385
5. MinK-RELATED PEPTIDES: COMMONALTIES AND IMPLICATIONS 386
5.1 Genetics and structure 386
5.2 Cell biology and function 387
6. ANSWERS, SOME OUTSTANDING ISSUES, CONCLUSIONS 387
7. ACKNOWLEDGEMENTS 389
8. REFERENCES 389
MinK and MinK-related peptide 1 (MiRP1) are integral membrane peptides with a single transmembrane span. These peptides are active only when co-assembled with pore-forming K+ channel subunits and yet their role in normal ion channel behaviour is obligatory. In the resultant complex the peptides establish key functional attributes: gating kinetics, single-channel conductance, ion selectivity, regulation and pharmacology. Co-assembly is required to reconstitute channel behaviours like those observed in native cells. Thus, MinK/KvLQT1 and MiRP1/HERG complexes reproduce the cardiac currents called IKs and IKr, respectively. Inherited mutations in KCNE1 (encoding MinK) and KCNE2 (encoding MiRP1) are associated with lethal cardiac arrhythmias. How these mutations change ion channel behaviour has shed light on peptide structure and function. Recently, KCNE3 and KCNE4 were isolated. In this review, we consider what is known and what remains controversial about this emerging superfamily.
Conserved geometrical base-pairing patterns in RNA
- NEOCLES B. LEONTIS, ERIC WESTHOF
-
- Published online by Cambridge University Press:
- 01 November 1998, pp. 399-455
-
- Article
- Export citation
-
1. INTRODUCTION 399
2. DEFINITIONS 401
3. CIS BASEPAIRS 410
3.1 Cis Watson–Crick/Watson–Crick 410
3.2 Wobble pairings 411
3.3 Cis Watson–Crick/Hoogsteen pairings 416
3.4 Bifurcated pairings 417
3.5 Cis open and water-inserted 421
4. TRANS BASEPAIRS 423
4.1 Trans Watson–Crick/Watson–Crick 423
4.2 Trans wobble pairs 424
4.3 Trans Watson–Crick/Hoogsteen pairs 424
4.4 Trans Hoogsteen/Hoogsteen pairs 430
4.5 Trans bifurcated pairings 432
5. SHALLOW-GROOVE PAIRINGS 432
5.1 Hoogsteen/Shallow-groove pairs 433
5.2 Watson–Crick/Shallow-groove pairings 438
5.3 Shallow-groove/Shallow-groove pairings 440
6. SIDE-BY-SIDE BASES 446
7. DEFINING A LIBRARY OF ISOSTERIC PAIRINGS 446
8. CONCLUSIONS 451
9. ACKNOWLEDGEMENTS 452
10. REFERENCES 452
RNA molecules fold into a bewildering variety of complex 3D structures. Almost every new RNA structure obtained at high resolution reveals new, unanticipated structural motifs, which we are rarely able to predict at the current stage of our theoretical understanding. Even at the most basic level of specific RNA interactions – base-to-base pairing – new interactions continue to be uncovered as new structures appear. Compilations of possible non-canonical base-pairing geometries have been presented in previous reviews and monographs (Saenger, 1984; Tinoco, 1993). In these compilations, the guiding principle applied was the optimization of hydrogen-bonding. All possible pairs with two standard H-bonds were presented and these were organized according to symmetry or base type. However, many of the features of RNA base-pairing interactions that have been revealed by high-resolution crystallographic analysis could not have been anticipated and, therefore were not incorporated into these compilations. These will be described and classified in the present review. A recently presented approach for inferring basepair geometry from patterns of sequence variation (Gautheret & Gutell, 1997) relied on the 1984 compilation of basepairs (Saenger, 1984), and was extended to include all possible single H-bond combinations not subject to steric clashes. Another recent review may be consulted for a discussion of the NMR spectroscopy and thermodynamic effects of non-canonical (‘mismatched’) RNA basepairs on duplex stability (Limmer, 1997).