S-layer

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• In Gram-negative bacteria, S-layers are associated to the lipopolysaccharides via protein–carbohydrate interactions.
• In Gram-positive bacteria whose S-layers often contain surface layer homology (SLH) domains, the binding occurs to the peptidoglycan and to a secondary cell wall polymer (e.g., teichoic acids). In the absence of SLH domains, the binding occurs via electrostatic interactions between the positively charged N-terminus of the S-layer protein and a negatively charged secondary cell wall polymer. In Lactobacilli the binding domain may be located at the C-terminus.
• In Gram-negative archaea, S-layer proteins possess a hydrophobic anchor that is associated with the underlying lipid membrane.
• In Gram-positive archaea, the S-layer proteins bind to pseudomurein or to methanochondroitin.

For many bacteria, the S-layer represents the outermost interaction zone with their respective environment.{{cite journal|last1=Sleytr|first1=UB|last2=Beveridge|first2=TJ|title=Bacterial S-layers|journal=Trends Microbiol.|volume=7|issue=6|pages=253–260|year=1999|pmid=10366863|doi=10.1016/s0966-842x(99)01513-9}} Its functions are very diverse and vary from species to species. In many archaeal species the S-layer is the only cell wall component and, therefore, is important for mechanical and osmotic stabilization.{{Cite journal |last1=Pfeifer |first1=Kevin |last2=Ehmoser |first2=Eva-Kathrin |last3=Rittmann |first3=Simon K.-M. R. |last4=Schleper |first4=Christa |last5=Pum |first5=Dietmar |last6=Sleytr |first6=Uwe B. |last7=Schuster |first7=Bernhard |date=2022-07-21 |title=Isolation and Characterization of Cell Envelope Fragments Comprising Archaeal S-Layer Proteins |journal=Nanomaterials |language=en |volume=12 |issue=14 |page=2502 |doi=10.3390/nano12142502 |pmid=35889727 |pmc=9320373 |issn=2079-4991 |doi-access=free }} The S-layer is considered to be porous, which contributes to many of its functions. A most relevant general function of S-layers of both, bacteria and archaea, seems to be their excellent anti-fouling properties.{{cite journal |vauthors=Rothbauer M, Küpcü S, Sticker D, Sleytr UB, Ertl P |date=2013 |title=Exploitation of S-layer Anisotropy: pH-dependent Nanolayer Orientation for Cellular Micropatterning |journal=ACS Nano |volume=7 |issue=9 |pages=8020–8030 |doi=10.1021/nn403198a |pmid=24004386 }} In Archaea that possess S-Layers as the exclusive cell wall component, a general function of S-layer lattices is that of a cell shape-determining/maintaining scaffold.{{cite journal | vauthors = Messner P, Pum D, Sára M, Stetter KO, Sleytr UB | date = 1986 | title = Ultrastructure of the cell envelope of the archaebacteria Thermoproteus tenax and Thermoproteus neutrophilus | journal = J. Bacteriol. | volume = 166 | issue = 3 | pages = 1046–1054| doi=10.1128/jb.166.3.1046-1054.1986| pmid = 3086286 | pmc = 215230 }}{{cite journal | vauthors = Zink IA, Pfeifer K, Wimmer E, Sleytr UB, Schuster B, Schleper C | date = 2019 | title = CRISPR-mediated gene silencing reveals involvement of the archaeal S-layer in cell division and virus infection | journal = Nat. Commun. | volume = 10 | page = 4797| doi=10.1038/s41467-019-12745-x | pmid = 31641111 | pmc = 6805947 | bibcode = 2019NatCo..10.4797Z }} For an overview of functions of S-layers, see. The spectrum of functions associated with S-layers include:

• protection against bacteriophages, Bdellovibrios, and phagocytosis
• resistance against low pH
• barrier against high-molecular-weight substances (e.g., lytic enzymes)
• adhesion (for glycosylated S-layers)
• stabilization of the membrane (e.g. the SDBC in Deinococcus radiodurans) {{cite journal |vauthors=Farci D, Slavov C, Tramontano E, Piano D |date=2016 |title=The S-layer Protein DR_2577 Binds Deinoxanthin and under Desiccation Conditions Protects against UV-Radiation in Deinococcus radiodurans |journal=Frontiers in Microbiology |volume=7 |page=155 |doi=10.3389/fmicb.2016.00155 |pmid=26909071 |pmc=4754619 |doi-access=free }}{{cite journal |vauthors=Farci D, Slavov C, Piano D |date=2018 |title=Coexisting properties of thermostability and ultraviolet radiation resistance in the main S-layer complex of Deinococcus radiodurans |journal=Photochem Photobiol Sci |volume=17 |issue=1 |pages=81–88 |doi=10.1039/c7pp00240h |pmid=29218340 |bibcode=2018PcPbS..17...81F |doi-access=free }}
• resistance against electromagnetic stress (e.g. ionizing radiations and high temperatures) {{cite journal |vauthors=Farci D, Slavov C, Tramontano E, Piano D |date=2016 |title=The S-layer Protein DR_2577 Binds Deinoxanthin and under Desiccation Conditions Protects against UV-Radiation in Deinococcus radiodurans |journal=Frontiers in Microbiology |volume=7 |page=155 |doi=10.3389/fmicb.2016.00155 |pmid=26909071 |pmc=4754619 |doi-access=free }}{{cite journal |vauthors=Farci D, Slavov C, Piano D |date=2018 |title=Coexisting properties of thermostability and ultraviolet radiation resistance in the main S-layer complex of Deinococcus radiodurans |journal=Photochem Photobiol Sci |volume=17 |issue=1 |pages=81–88 |doi=10.1039/c7pp00240h |pmid=29218340 |bibcode=2018PcPbS..17...81F |doi-access=free }}
• provision of adhesion sites for exoproteins {{cite journal |vauthors = Egelseer E, Schocher I, Sára M, Sleytr UB |date = 1995 | title= The S-layer from Bacillus stearothermophilus DSM 2358 functions as adhesion site for a high-molecular-weight amylase | journal = J Bacteriol | volume = 177 | issue = 6 | pages = 1444–1451 | doi=10.1128/jb.177.6.1444-1451.1995 |pmid = 7533757 | pmc = 176758 }}
• provision of a periplasmic compartment in Gram-positive prokaryotes together with the peptidoglycan and the cytoplasmic membranes
• biomineralization{{cite journal |vauthors=Schultze-Lam S, Harauz G, Beveridge TJ |date=1992 |title=Participation of a cyanobacterial S layer in fine-grain mineral formation|journal=J. Bacteriol. |volume=174 |issue=24 |pages=7971–7981 |doi=10.1128/jb.174.24.7971-7981.1992 |pmid=1459945 |pmc=207533 }}{{cite journal |vauthors=Shenton W, Pum D, Sleytr UB, Mann S |date=1997 |title=Synthesis of CdS superlattices using self-assembled bacterial S-layers |journal=Nature |volume=389 |issue= 6651|pages=585–587 |doi=10.1038/39287 |s2cid=4317884 }}{{cite journal |vauthors=Mertig M, Kirsch R, Pompe W, Engelhardt H |date=1999 |title=Fabrication of highly oriented nanocluster arrays by biomolecular templating |journal=Eur. Phys. J. D |volume=9 |issue=1 |pages=45–48 |doi=10.1007/s100530050397 |bibcode=1999EPJD....9...45M |s2cid=120507258 }}
• molecular sieve and barrier function{{cite journal |vauthors=Sára M, Sleytr, UB |date=1987 |title= Production and characteristics of ultrafiltration membranes with uniform pores from two-dimensional arrays of proteins |journal=J. Membr. Sci. |volume=33 |issue=1 |pages=27–49 |doi=10.1016/S0376-7388(00)80050-2 }}{{cite journal |last1=von Kügelgen |first1=Andriko |last2=Cassidy |first2=C. Keith |last3=van Dorst |first3=Sofie |last4=Pagani |first4=Lennart L. |last5=Batters |first5=Christopher |last6=Ford |first6=Zephyr |last7=Löwe |first7=Jan |last8=Alva |first8=Vikram |last9=Stansfeld |first9=Phillip J. |last10=Bharat |first10=Tanmay A. M. |title=Membraneless channels sieve cations in ammonia-oxidizing marine archaea |journal=Nature |date=6 June 2024 |volume=630 |issue=8015 |pages=230–236 |doi=10.1038/s41586-024-07462-5 |doi-access=free|pmid=38811725 |pmc=11153153 |bibcode=2024Natur.630..230V }}{{cite journal |vauthors=Schuster B, Sleytr UB |date=2021 |title=S-Layer Ultrafiltration Membranes |journal=Membranes |volume=11 |issue=4 |page=275 |doi=10.3390/membranes11040275 |pmid=33918014 |pmc=8068369 |doi-access=free }}

A great example of a bacterium which utilizes the biological functions of the S-layer is Clostridioides difficile. In C. difficile, the S-layer has helped with biofilm formation, host cell adhesion, and immunomodulation through cell signaling of the host response.{{Cite journal |last1=Ormsby |first1=Michael J. |last2=Vaz |first2=Filipa |last3=Kirk |first3=Joseph A. |last4=Barwinska-Sendra |first4=Anna |last5=Hallam |first5=Jennifer C. |last6=Lanzoni-Mangutchi |first6=Paola |last7=Cole |first7=John |last8=Chaudhuri |first8=Roy R. |last9=Salgado |first9=Paula S. |last10=Fagan |first10=Robert P. |last11=Douce |first11=Gillian R. |date=2023-06-29 |title=An intact S-layer is advantageous to Clostridioides difficile within the host |journal=PLOS Pathogens |language=en |volume=19 |issue=6 |pages=e1011015 |doi=10.1371/journal.ppat.1011015 |issn=1553-7374 |pmc=10310040 |pmid=37384772 |doi-access=free }}

While ubiquitous among Archaea, and common in bacteria, the S-layers of diverse organisms have unique structural properties, including symmetry and unit cell dimensions, due to fundamental differences in their constituent building blocks.{{cite book |vauthors=Pavkov-Keller T, Howorka S, Keller W |title=Molecular Assembly in Natural and Engineered Systems |date=2011 |chapter=The structure of bacterial S-layer proteins |series=Progress in Molecular Biology and Translational Science V. 103 |volume=103 |pages=73–130 |doi=10.1016/B978-0-12-415906-8.00004-2 |pmid=21999995 |isbn=978-0-12-415906-8 }} Sequence analyses of S-layer proteins have predicted that S-layer proteins have sizes of 40-200 kDa and may be composed of multiple domains some of which may be structurally related. Since the first evidence of a macromolecular array on a bacterial cell wall fragment in the 1950s,{{cite journal |author=Houwink, AL |title=A macromolecular mono-layer in the cell wall of Spirillum spec. |journal=Biochim Biophys Acta |volume=10 |issue=3 |pages=360–6|year=1953 |pmid=13058992 |doi=10.1016/0006-3002(53)90266-2}} S-layer structures have been investigated extensively by electron microscopy. These studies have provided useful information on overall S-layer morphology.

In general, S-layers exhibit either oblique (p1, p2), square (p4) or hexagonal (p3, p6) lattice symmetry. Depending on the lattice symmetry, each morphological unit of the S-layer is composed of one (p1), two (p2), three (p3), four (p4), or six (p6) identical protein subunits. The center-to-center spacing (or unit cell dimensions) between these subunits range from 4 to 35 nm.

For example, high-resolution structures of an archaeal S-layer protein (MA0829 from Methanosarcina acetivorans C2A) of the Methanosarcinales S-layer Tile Protein family and a bacterial S-layer protein (SbsB), from Geobacillus stearothermophilus PV72, have been determined by X-ray crystallography.{{cite journal |vauthors=Arbing MA, Chan S, Shin A, Phan T, Ahn CJ, Rohlin L, Gunsalus RP |title=Structure of the surface layer of the methanogenic archaean Methanosarcina acetivorans. |journal=Proc Natl Acad Sci U S A |volume=109 |issue=29 |pages=11812–7 |year=2012 |pmid=22753492 |doi=10.1073/pnas.1120595109 |pmc=3406845|bibcode=2012PNAS..10911812A |doi-access=free }}{{cite journal |vauthors=Baranova E, Fronzes R, Garcia-Pino A, Van Gerven N, Papapostolou D, Péhau-Arnaudet G, Pardon E, Steyaert J, Howorka S, Remaut H |title=SbsB structure and lattice reconstruction unveil Ca2+ triggered S-layer assembly |journal=Nature |volume=487 |issue=7405 |pages=119–22 |year=2012 |pmid=22722836 |doi=10.1038/nature11155|bibcode=2012Natur.487..119B |s2cid=4389187 |url=https://biblio.vub.ac.be/vubirfiles/5658510/nature11155.pdf }} In contrast with existing crystal structures, which have represented individual domains of S-layer proteins or minor proteinaceous components of the S-layer, the MA0829 and SbsB structures have allowed high resolution models of the M. acetivorans and G. stearothermophilus S-layers to be proposed. These models exhibit hexagonal (p6) and oblique (p2) symmetry, for M. acetivorans and G. stearothermophilus S-layers, respectively, and their molecular features, including dimensions and porosity, are in good agreement with data from electron microscopy studies of archaeal and bacterial S-layers.

Finally, in connection with questions of structure-function investigations on S-layers, it should be mentioned that the recent introduction of SymProFold, which utlizes the high accuracy of AlphaFold-Multimer predictions to derive symmetrical assemblies from protein sequeces has proven to be a groundbreaking method for the accurate structural prediction of S-layer arrays. The predicted models could be vallidated using available experimental data at the cellular level, and additional crystal structures were obtained to confirm the symmetry and interfaces of numerous SymProFold assemblies. Thus, this methodological approach to the structural elucidation of S-layers opens possibilities for exploring functionalities and designing targeted applications in diverse fields such as nanotechnology, biotechnology, nanomedicine, and environmental sciences.{{cite journal |vauthors=Ilk N, Egelseer EM, Sleytr UB |date=2011 |title=S-layer fusion proteins - construction principles and applications |journal=Curr. Opin. Biotechnol. |volume=22 |issue=6 |pages=824–831 |doi=10.1016/j.copbio.2011.05.510 |pmc=3271365 |pmid=21696943 }}

Assembly of a highly ordered coherent monomolecular S-layer array on a growing cell surface requires a continuous synthesis of a surplus of S-layer proteins and their translocation to sites of lattice growth.{{cite journal |vauthors=Fagan RP, Fairweather NF |date=2014 |title=Biogenesis and functions of bacterial S-layers |url= http://eprints.whiterose.ac.uk/97080/1/Fagan%20and%20Fairweather_for%20deposit.pdf|journal=Nature Reviews. Microbiology |volume=12 |issue=3 |pages=211–222 |doi=10.1038/nrmicro3213 |pmid=24509785 |s2cid=24112697 }} Moreover, information concerning this dynamic process were obtained from reconstitution experiments with isolated S-layer subunits on cell surfaces from which they had been removed (homologous reattachment) or on those of other organisms (heterologous reattachment).{{cite journal |author=Sleytr UB |date=1975 |title=Heterologous reattachment of regular arrays of glycoproteins on bacterial surfaces |journal=Nature |volume=257 |issue= 5525|pages=400–402 |doi=10.1038/257400a0 |pmid= 241021|bibcode=1975Natur.257..400S |s2cid=4298430 }}

S-layer proteins have the natural capability to self-assemble into regular monomolecular arrays in solution and at interfaces, such as solid supports, the air-water interface, lipid films, liposomes, emulsomes, nanocapsules, nanoparticles or micro beads.

{{cite journal |vauthors=Pum D, Sleytr UB |date=2014 |title=Reassembly of S-layer proteins |journal=Nanotechnology |volume=25 |issue= 31|page=312001 |doi=10.1088/0957-4484/25/31/312001 |pmid= 25030207|bibcode=2014Nanot..25E2001P |s2cid=39889746 }}{{cite journal |vauthors=Schuster B, Sleytr UB |date=2014 |title=Biomimetic interfaces based on S-layer proteins, lipid membranes and functional biomolecules |url=http://rsif.royalsocietypublishing.org/node/7191.full |journal=J. R. Soc. Interface |volume=11 |issue=96 |page=20140232 |doi=10.1098/rsif.2014.0232 |pmid=24812051 |pmc=4032536 }} S-layer crystal growth follows a non-classical pathway in which a final refolding step of the S-layer protein is part of the lattice formation.{{cite journal |vauthors=Chung S, Shin SH, Bertozzi CR, De Yoreo JJ |date=2010 |title=Self-catalyzed growth of S layers via an amorphous-to-crystalline transition limited by folding kinetics |journal=Proc. Natl. Acad. Sci. USA |volume=107 |issue=38 |pages=16536–16541 |doi=10.1073/pnas.1008280107 |pmid=20823255 |pmc=2944705 |bibcode=2010PNAS..10716536C |doi-access=free }}{{cite journal |vauthors=Shin SH, Chung S, Sanii B, Comolli LR, Bertozzi CR, De Yoreo JJ |date=2012 |title=Direct observation of kinetic traps associated with structural transformations leading to multiple pathways of S-layer assembly |journal=Proc. Natl. Acad. Sci. USA |volume=109 |issue= 32|pages=12968–12973 |doi=10.1073/pnas.1201504109 |pmid=22822216 |pmc=3420203 |bibcode=2012PNAS..10912968S |doi-access=free }}

Native S-layer proteins have already been used three decades ago in the development of biosensors and ultrafiltration membranes. Subsequently, S-layer fusion proteins with specific functional domains (e.g. enzymes, ligands, mimotopes, antibodies or antigens) allowed to investigate completely new strategies for functionalizing surfaces in the life sciences, such as in the development of novel affinity matrices, mucosal vaccines, biocompatible surfaces, micro carriers and encapsulation systems, or in the material sciences as templates for biomineralization.{{cite journal |doi=10.1016/S0168-6445(97)00044-2 |vauthors=Sleytr U, Bayley H, Sára M, Breitwieser A, Küpcü S, Mader C, Weigert S, Unger F, Messner P, Jahn-Schmid B, Schuster B, Pum D, Douglas K, Clark N, Moore J, Winningham T, Levy S, Frithsen I, Pankovc J, Beale P, Gillis H, Choutov D, Martin K |title=Applications of S-layers |journal=FEMS Microbiol. Rev. |volume=20 |issue=1–2 |pages=151–75 |year=1997 |doi-broken-date=29 April 2025 |pmid=9276930}}{{cite journal | vauthors = Qing R, Xue MT, Zhao JY, Wu LD, Breitwieser A, Smorodina E, Schubert T, Azzellino G, Jin D, Kong J, Palacios T, Sleytr UB, Zhang SG |date=2023 | title= Scalable biomimetic sensing system with membrane receptor dual-monolayer probe and graphene transistor arrays | journal = Science Advances | volume = 9 | issue = 29 | pages = eadf1402 | doi=10.1126/sciadv.adf1402|pmid=37478177 |pmc=10361598 |bibcode=2023SciA....9F1402Q | hdl = 10852/108278 | hdl-access = free }}

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Category:Cell anatomy

Category:Membrane biology