The three‐dimensional structure of porin from <i>Rhodobacter capsulatus</i> at 3 Å resolution

Weiss, M.S.; Wacker, Thomas; Weckesser, Jürgen; Weite, W.; Schulz, Georg E.

doi:10.1016/0014-5793(90)80942-c

Cited by 208 publications

(123 citation statements)

References 34 publications

Supporting

Mentioning

117

Contrasting

Order By: Relevance

“…Here, suffice it to say that these criteria are probably not too highly restrictive if account is taken of the likelihood that the interface between the bilayer and the water in the amyloid core is not infinitely sharp, as it is generally implicitly assumed to be. These criteria might be expected to be closely similar to those for the membrane-intercalated portions of the ␤-strands of the ␤-barrel proteins, such as the porins (14)(15)(16), because the successive amino acids of the ␤-strands traversing the membrane have environments at the bilayer͞ water interface that are closely similar for the two structures. Different amino acid sequences for different ␤-amyloids may also allow some to adopt slightly different Perutz et al stable structures containing 19 or 21 residues per turn as well as 20 (as with A␤ 1-40 and A␤ 1-42).…”

Section: Discussionmentioning

confidence: 94%

Evidence that Perutz's double-β-stranded subunit structure for β-amyloids also applies to their channel-forming structures in membranes

Singer

Dewji

2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Although there is a growing body of evidence that different amyloidoses may have a similar molecular mechanism in common, the many details of this mechanism are not understood. In this study, we propose that there is a common molecular structure of the primary agents of these diseases, namely a small oligomer of Perutz's cylindrical double-␤-stranded subunit for polyglutamine and that this structure, which contains a central water-filled core, can spontaneously integrate into the bilayers of membranes to form aqueous pores. We suggest that this ability to produce permeable channels in appropriate neuronal membranes is a key element in the toxicity of the ␤-amyloids. One strong criterion for the stability of the Perutz structure for an amyloid is that it contain Ϸ40 or more amino acid residues. We show here that the neurotoxic A␤ amyloids 1-40 and 1-42, related to Alzheimer's disease, spontaneously enter the membranes of intact erythrocytes and cause their lysis but that A␤ 1-38 and A␤ 1-35, which are not neurotoxic, have no observable effects on erythrocytes, supporting our proposal. Other aspects of the proposed mechanism of cytotoxicity of the ␤-amyloids are explored.A large and continually increasing number of diseases, including the neurodegenerative syndromes Alzheimer's disease (AD), Parkinson's disease, and Huntington's disease as well as the spongiform encephalopathies (prion diseases) such as mad cow disease are all associated with the formation of characteristic proteinaceous components that can form aggregates and͞or fibrils under appropriate conditions in water. These components are collectively called ␤-amyloids. In these fibrils and aggregates, the ␤-amyloids are all largely in the ␤-conformation and can be stained with Congo red, which reveals that they contain a hydrophobic environment that bonds the dye. These extensively aggregated ␤-amyloid structures are present at equilibrium with small water-soluble species containing from one to a dozen or so of the repeating subunits of the ␤-amyloid, each bonded noncovalently to its neighboring subunits. It is widely accepted that some form of the particular ␤-amyloid is critically involved in the neurotoxicity of its associated disease, but the detailed mechanisms for this involvement have not been elucidated. In previous years, it was vigorously disputed whether the larger aggregates or one or more of the smaller soluble species of ␤-amyloids are the primary toxic components, but in the last few years, several studies (see refs. 1-4) have clearly implicated the smaller soluble species in the toxic process. The fibrils and aggregates may serve as storage depots of longer ␤-amyloid chains rather than of the shorter soluble forms. Close Similarities in the Structures and Functions of Different ␤-AmyloidsOne of the most remarkable of these recent studies is that of Kayed et al. (3). Working with A␤ 1-40, which is a ␤-amyloid associated with AD, Kayed et al. reported the production of a MAb that binds to, and inhibits the toxicity of, water-soluble intermed...

show abstract

Section: Discussionmentioning

confidence: 94%

Evidence that Perutz's double-β-stranded subunit structure for β-amyloids also applies to their channel-forming structures in membranes

Singer

Dewji

2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The PDB entries used for the structural analysis were Zomf, matrix porin from E. coli; Ipho, phosphoporin from E. coli (Cowan et al, 1992); Iprn, porin from R. blastica (Kreusch et al, 1994); 2por from R. capsulatus (Weiss et al, 1990(Weiss et al, , 1991bWeiss & Schulz, 1992); Imal, maltoporin from E. coli (Schirmer et al, 1995). In all but 2omf, the PDB entries contained the coordinates of only one monomer.…”

Section: Materials and Methods: Pdb Filesmentioning

confidence: 99%

Architecture of β‐barrel membrane proteins: Analysis of trimeric porins

et al. 1998

View full text Add to dashboard Cite

Abstract:We have analyzed the known three-dimensional structures of trimeric porins from bacterial outer membranes. The distribution of surface-exposed residues in a direction perpendicular to the membrane is similar to that in helical membrane proteins, with aliphatic residues concentrated in the central 20 8, of the bilayer. Outside these residues is a layer of aromatic residues, followed by polar and charged residues. Residues in the trimer interface are more conserved than residues not in the interface. By comparing the interface and noninterface residues, an interface preference scale has been derived that may be used as a basis for predicting interface surfaces in monomer models.Keywords: P-barrel; membrane protein; porin; three-dimensional structure As far as is known from high-resolution structural data, integral membrane proteins belong either to the helix-bundle or the /?-barrel class (von Heijne, 1997). In both cases, hydrophobic amino acids provide the interface to the surrounding lipid bilayer, but, beyond this, the two architectures are very different. Thus, while transmembrane a-helices are more or less uniformly hydrophobic (Bowie, 1997;Wallin et al., 1997), transmembrane P-strands tend to be amphiphilic, with polar and charged residues projecting into a central pore. Moreover, most transmembrane a-helices are believed to be individually stable in the bilayer (Hunt et al., 1997;Popot & Engelman, 1997) whereas individual transmembrane @strands certainly are not. Their respective modes of membrane insertion are thus very different (von Heijne, 1997).All P-barrel outer membrane proteins (porins), for which highresolution structures are available form oligomers, and, thus, bury part of their outer surface in a protein-protein interface (Fig. 1). In contrast to water-soluble proteins, little is known about the factors that drive the association between protein subunits in a lipid environment. To provide a basis for understanding general aspects of membrane protein structure, we have analyzed the known highReprint requests to: Arne Elofsson, Department of Biochemistry, Stockholm University, s-106 91 Stockholm, Sweden; e-mail: arne@biokemi.su.se. resolution porin structures in terms of which kinds of residues are exposed to the lipid environment, buried within monomers, exposed to the central pore and buried between subunits. In particular, we show that subunit interfaces can be roughly identified on the basis of amino acid composition and residue conservation, suggesting that it may be possible to extend current methods for predicting transmembrane P-strands and overall monomer fold (Schirmer & Cowan, 1993;Gromiha et al., 1997) to also include the oligomeric structure. Table 1 presents some basic statistics for the proteins used in this study. The porins of known structure can be divided into three groups according to the number of P-strands forming the pore. Porins from Rhodopseudomonas blastica (Ipm) and from Rhodobacter capsulatus (2por and 3por, two different crystal forms of the same protein) both...

show abstract

“…The analysis of crystal form-B was started using a partially refined medium resolution model [18] which at this point consisted of 310 residues with an 'X-ray sequence' that had been read from the electron density map, Because of the close packing relationship between crystal forms-A and -I3, the starting model as defined in crystal form-A was positioned into crystal form-B solely by shortening the unit cell axes from A-to B.lengths, The model position was then improved by using the rigid body refinement option of the program package XPLOR [22] in the resolution range 10-6 ,~, on our VaxStation-3100, Within 40 cycles the R-factor dropped from 49°70 to 37% showin~ that the model was placed correctly. In tile subsequent refinement we used standard XPLOR protocols on a CRAY-YMP (HLRZ, JiJlich), extended the resolution range gradually to 2.…”

Section: Methodsmentioning

confidence: 99%

“…dimensional crystals of porin have been studied by electron microscopic methods yielding the general shape of the molecule [8][9][10][11][12][13], Also, a number of three-dimensional perth crystals suitable for X-ray diffraction analysis have been reported [14][15][16][17]. The crystal structure of the porin from Rhodobacter capsulatus is known at medium resolution [18], Using a related, new crystal form [19] and the amino acid sequence (E. Schultz, A. Kreusch, U, Nestel and G.E. Schulz, unpublished results) the resolution of the structure analysis has now been extended to 1.8 A.…”

Section: Introductionmentioning

confidence: 99%

The structure of porin from Rhodobacter capsulatus at 1.8 Å resolution

et al. 1991

Self Cite

View full text Add to dashboard Cite

Volume 2g0, number 2, 379~3~ FEELS 09~)4 '~ 1991 Feder#tton of I~aroF~an ltio,~heml¢~l So~iett,¢i 0014~17~1~'91t$] Tile structure of the perth front Rlmd.b~trt¢r ¢cJpxlqhuu~ was determin¢d at a resolution of !,~ A. The analysi=t stalled from a eJt~sety r~laled ¢rytl¢il ~tructur~ thai had been sol~'ed at a medium resolution of 3 A using mulliple isotnorphou~ replacement ttnd solvent llattenin//,. The new structure contains the complete seq uent:e of.~0 ! amino acid residues, Refinement of the model is uoder ~¢~y; the present R.fa¢ior i~ 22,~ with ~ood geometry,Except for the len~lths of several loops, the resultinl~ chain fold corresponds to the medium r0soltttion model, The membrane cha,mel is lined by a larl/e naml:er of ionol|cnic side chains with ¢:haracttriliie segrel~ation ofdifl'~rently charged ~troups.

show abstract

The three‐dimensional structure of porin from Rhodobacter capsulatus at 3 Å resolution

Cited by 208 publications

References 34 publications

Evidence that Perutz's double-β-stranded subunit structure for β-amyloids also applies to their channel-forming structures in membranes

Evidence that Perutz's double-β-stranded subunit structure for β-amyloids also applies to their channel-forming structures in membranes

Architecture of β‐barrel membrane proteins: Analysis of trimeric porins

The structure of porin from Rhodobacter capsulatus at 1.8 Å resolution

Contact Info

Product

Resources

About