Alpha solenoid

The term "alpha solenoid" has been used somewhat inconsistently in the literature. As originally defined, alpha solenoids were composed of helix-turn-helix motifs that stacked into an open superhelix.{{cite journal|last1=Kobe|first1=Bostjan|last2=Kajava|first2=Andrey V|title=When protein folding is simplified to protein coiling: the continuum of solenoid protein structures|journal=Trends in Biochemical Sciences|date=October 2000|volume=25|issue=10|pages=509–515|doi=10.1016/S0968-0004(00)01667-4|pmid=11050437}} However, protein structural classification systems have used varying terminology; the Structural Classification of Proteins (SCOP) database describes these proteins using the term "alpha alpha superhelix". The CATH database uses the term "alpha horseshoe" {{cite web|title=CATH Topology "Alpha Horseshoe"|url=http://www.cathdb.info/cathnode/1.25}} for these proteins, and uses "alpha solenoid" for a somewhat different and more compact structure exemplified by the peridinin-chlorophyll binding protein.

Alpha solenoid proteins are composed of repeating structural units containing at least two alpha helices arranged in an antiparallel orientation. Often the repeating unit is a helix-turn-helix motif, but it can be more elaborate, as in variants with an additional helix in the turn segment. Alpha solenoids can be formed by several different types of helical tandem repeats, including HEAT repeats, Armadillo repeats, tetratricopeptide (TPR) repeats, leucine-rich repeats, and ankyrin repeats.

Alpha solenoids have unusual elasticity and flexibility relative to globular proteins. They are sometimes considered to occupy an intermediate position between globular proteins and fibrous structural proteins, distinct from the latter in part due to the alpha solenoids' lack of need for intermolecular interactions to maintain their structure. The extent of the curvature of an alpha solenoid superhelix varies considerably among the class, resulting in the ability of these proteins to form large, extended protein-protein interaction surfaces or to form deep concave areas for binding globular proteins.

Because they are composed of repeating relatively short subunits, alpha solenoids can acquire additional subunits relatively easily, resulting in new interaction surface properties. As a result, known alpha solenoid proteins vary substantially in length.

Alpha solenoids feature prominently in the proteins making up the nuclear pore complex (NPC); alpha solenoid and beta propeller domains together account for up to half of the core NPC scaffold by mass. A large number of the conserved nucleoporin proteins forming the NPC are either alpha solenoid proteins or consist of a beta propeller domain at the N-terminus and an alpha solenoid at the C-terminus.{{cite journal|last1=Alber|first1=Frank|last2=Dokudovskaya|first2=Svetlana|last3=Veenhoff|first3=Liesbeth M.|last4=Zhang|first4=Wenzhu|last5=Kipper|first5=Julia|last6=Devos|first6=Damien|last7=Suprapto|first7=Adisetyantari|last8=Karni-Schmidt|first8=Orit|last9=Williams|first9=Rosemary|last10=Chait|first10=Brian T.|last11=Sali|first11=Andrej|last12=Rout|first12=Michael P.|title=The molecular architecture of the nuclear pore complex|journal=Nature|date=29 November 2007|volume=450|issue=7170|pages=695–701|doi=10.1038/nature06405|pmid=18046406|bibcode=2007Natur.450..695A|s2cid=4431057}}{{cite journal|last1=Devos|first1=Damien|last2=Dokudovskaya|first2=Svetlana|last3=Alber|first3=Frank|last4=Williams|first4=Rosemary|last5=Chait|first5=Brian T|last6=Sali|first6=Andrej|last7=Rout|first7=Michael P|last8=Greg Petsko|title=Components of Coated Vesicles and Nuclear Pore Complexes Share a Common Molecular Architecture|journal=PLOS Biology|date=2 November 2004|volume=2|issue=12|pages=e380|doi=10.1371/journal.pbio.0020380|pmid=15523559|pmc=524472 |doi-access=free }} This latter domain architecture also occurs in clathrin and Sec31, and was thought to be unique to eukaryotes,{{cite journal|last1=Antonin|first1=Wolfram|last2=Mattaj|first2=Iain W.|title=Nuclear pore complexes: Round the bend?|journal=Nature Cell Biology|date=January 2005|volume=7|issue=1|pages=10–12|doi=10.1038/ncb0105-10|pmid=15632943|s2cid=9909704}} though a few examples have been reported in planctomycetes.{{cite journal|last1=Santarella-Mellwig|first1=Rachel|last2=Franke|first2=Josef|last3=Jaedicke|first3=Andreas|last4=Gorjanacz|first4=Matyas|last5=Bauer|first5=Ulrike|last6=Budd|first6=Aidan|last7=Mattaj|first7=Iain W.|last8=Devos|first8=Damien P.|last9=Schmid|first9=Sandra L.|title=The Compartmentalized Bacteria of the Planctomycetes-Verrucomicrobia-Chlamydiae Superphylum Have Membrane Coat-Like Proteins|journal=PLOS Biology|date=19 January 2010|volume=8|issue=1|pages=e1000281|doi=10.1371/journal.pbio.1000281|pmid=20087413|pmc=2799638 |doi-access=free }}

File:1b89 clathrin heavy chain leg.png heavy chain leg segment showing helical repeats, with the N-terminus in blue at left and the C-terminus in red at right.{{cite journal|last1=Ybe|first1=Joel A.|last2=Brodsky|first2=Frances M.|last3=Hofmann|first3=Kay|last4=Lin|first4=Kai|last5=Liu|first5=Shu-Hui|last6=Chen|first6=Lin|last7=Earnest|first7=Thomas N.|last8=Fletterick|first8=Robert J.|last9=Hwang|first9=Peter K.|title=Clathrin self-assembly is mediated by a tandemly repeated superhelix|journal=Nature|date=27 May 1999|volume=399|issue=6734|pages=371–375|doi=10.1038/20708|pmid=10360576|bibcode=1999Natur.399..371Y|s2cid=4406014}}]]

Vesicle coat proteins frequently contain alpha solenoids and share common domain architecture with some NPC proteins. Three major coat complexes involved in distinct cellular pathways all contain alpha solenoid proteins: the clathrin/adaptin complex, which buds vesicles from the plasma membrane and is involved in endocytosis; the COPI complex, which buds vesicles from the Golgi apparatus and is associated with retrograde transport; and the COPII complex, which buds vesicles from the endoplasmic reticulum and is associated with anterograde transport.{{cite journal|last1=Lee|first1=Changwook|last2=Goldberg|first2=Jonathan|title=Structure of Coatomer Cage Proteins and the Relationship among COPI, COPII, and Clathrin Vesicle Coats|journal=Cell|date=July 2010|volume=142|issue=1|pages=123–132|doi=10.1016/j.cell.2010.05.030|pmid=20579721|pmc=2943847}}

Due to their propensity for forming large interaction surfaces well-suited to protein-protein interactions, and their flexible surfaces permitting binding of various cargo molecules, alpha solenoid proteins commonly function as transport proteins, particularly in transport between the nucleus and the cytoplasm. For example, the beta-karyopherin superfamily consists of alpha solenoid proteins formed from HEAT repeats; importin beta is a member of this family, and its adaptor protein importin alpha is an alpha solenoid formed from Armadillo repeats.{{cite journal|last1=Forwood|first1=Jade K.|last2=Lange|first2=Allison|last3=Zachariae|first3=Ulrich|last4=Marfori|first4=Mary|last5=Preast|first5=Callie|last6=Grubmüller|first6=Helmut|last7=Stewart|first7=Murray|last8=Corbett|first8=Anita H.|last9=Kobe|first9=Bostjan|title=Quantitative Structural Analysis of Importin-β Flexibility: Paradigm for Solenoid Protein Structures|journal=Structure|date=September 2010|volume=18|issue=9|pages=1171–1183|doi=10.1016/j.str.2010.06.015|pmid=20826343|hdl=11858/00-001M-0000-0027-C07B-1|hdl-access=free}} Transporters of other molecules, such as RNA, can also be of alpha solenoid architecture, as in exportin-5{{cite journal|last1=Katahira|first1=Jun|last2=Yoneda|first2=Yoshihiro|title=Nucleocytoplasmic Transport of MicroRNAs and Related Small RNAs|journal=Traffic|date=November 2011|volume=12|issue=11|pages=1468–1474|doi=10.1111/j.1600-0854.2011.01211.x|pmid=21518166|s2cid=38777924 |doi-access=}} or pentatricopeptide-repeat-containing RNA-binding proteins, which are particularly common in plants.{{cite journal|last1=Barkan|first1=Alice|last2=Rojas|first2=Margarita|last3=Fujii|first3=Sota|last4=Yap|first4=Aaron|last5=Chong|first5=Yee Seng|last6=Bond|first6=Charles S.|last7=Small|first7=Ian|last8=Voytas|first8=Dan|title=A Combinatorial Amino Acid Code for RNA Recognition by Pentatricopeptide Repeat Proteins|journal=PLOS Genetics|date=16 August 2012|volume=8|issue=8|pages=e1002910|doi=10.1371/journal.pgen.1002910|pmid=22916040|pmc=3420917 |doi-access=free }}{{cite journal|last1=Barkan|first1=Alice|last2=Small|first2=Ian|title=Pentatricopeptide Repeat Proteins in Plants|journal=Annual Review of Plant Biology|date=29 April 2014|volume=65|issue=1|pages=415–442|doi=10.1146/annurev-arplant-050213-040159|pmid=24471833|doi-access=free}}

File:Pp2a 2iae chainABC 1b3u chainA.png. Subunit A, consisting of 15 HEAT repeats, is shown in rainbow color with the N-terminus in blue at bottom and the C-terminus in red at top. The regulatory subunit B, consisting of irregular pseudo-HEAT repeats, is shown in light blue. The catalytic subunit C is shown in tan. (All from {{PDB|2IAE}}.) Superposed is the unbound form of the regulatory subunit B in gray (from {{PDB|1B3U}}), illustrating the flexibility of this alpha solenoid protein. Conformational changes in HEAT repeat 11 result in flexing the C-terminal end of the protein to accommodate binding of the catalytic subunit.{{cite journal|last1=Groves|first1=Matthew R.|last2=Hanlon|first2=Neil|last3=Turowski|first3=Patric|last4=Hemmings|first4=Brian A.|last5=Barford|first5=David|title=The Structure of the Protein Phosphatase 2A PR65/A Subunit Reveals the Conformation of Its 15 Tandemly Repeated HEAT Motifs|journal=Cell|date=January 1999|volume=96|issue=1|pages=99–110|doi=10.1016/S0092-8674(00)80963-0|pmid=9989501|s2cid=14465060|doi-access=free}}]]

The protein-protein interaction capacity of alpha solenoid proteins also makes them well suited to function as regulatory proteins. For example, regulatory subunit A (also known as PR65) of protein phosphatase 2A is a HEAT-repeat alpha solenoid whose conformational flexibility regulates access to the enzyme binding site.{{cite journal|last1=Grinthal|first1=A.|last2=Adamovic|first2=I.|last3=Weiner|first3=B.|last4=Karplus|first4=M.|last5=Kleckner|first5=N.|title=PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis|journal=Proceedings of the National Academy of Sciences|date=25 January 2010|volume=107|issue=6|pages=2467–2472|doi=10.1073/pnas.0914073107|pmid=20133745|pmc=2823866|bibcode=2010PNAS..107.2467G|doi-access=free}}

Alpha solenoid proteins are found in all domains of life; however, their frequencies in different proteomes vary significantly. They are rare in viruses and bacteria, somewhat more common in archaea, and quite common in eukaryotes. Many of the eukaryotic alpha solenoid proteins have detectable homologs only in other eukaryotes and are often restricted even further, to the chordates. Prokaryotic alpha solenoid proteins are concentrated in particular taxa, notably the cyanobacteria and planctomycetes, which have unusually complex intracellular compartmentalization relative to most prokaryotes.

Evolutionary relationships between different alpha solenoid proteins are difficult to trace due to the low sequence homology of the repeats. Convergent evolution of similar protein structures from ancestrally unrelated proteins is thought to be significant in the evolutionary history of this fold class.

The nuclear pore complex is an extremely large protein complex that mediates transit into and out of the cell nucleus. Homologous structures from which the NPC might have evolved have not been detected in prokaryotic transmembrane transport proteins; however, it has been suggested that the NPC components show distinct homology to vesicle coat proteins found in clathrin/adaptin, COPI, and COPII complexes. Most distinctively, a shared domain architecture consisting of an N-terminal beta propeller and a C-terminal alpha solenoid has been detected in both NPC and coat proteins, suggesting a possible common origin. An ancestral "protocoatomer" that diversified to acquire derived characteristics of all four modern complexes has been proposed.{{cite journal|last1=Field|first1=Mark C|last2=Dacks|first2=Joel B|title=First and last ancestors: reconstructing evolution of the endomembrane system with ESCRTs, vesicle coat proteins, and nuclear pore complexes|journal=Current Opinion in Cell Biology|date=February 2009|volume=21|issue=1|pages=4–13|doi=10.1016/j.ceb.2008.12.004|pmid=19201590}}{{cite journal|last1=Dacks|first1=Joel B.|last2=Field|first2=Mark C.|last3=Buick|first3=Roger|last4=Eme|first4=Laura|last5=Gribaldo|first5=Simonetta|last6=Roger|first6=Andrew J.|last7=Brochier-Armanet|first7=Céline|last8=Devos|first8=Damien P.|title=The changing view of eukaryogenesis – fossils, cells, lineages and how they all come together|journal=Journal of Cell Science|date=26 September 2016|pages=3695–3703|doi=10.1242/jcs.178566|volume=129|issue=20|pmid=27672020|doi-access=free|hdl=10261/163440|hdl-access=free}}{{cite journal|last1=Promponas|first1=Vasilis J.|last2=Katsani|first2=Katerina R.|last3=Blencowe|first3=Benjamin J.|last4=Ouzounis|first4=Christos A.|title=Sequence evidence for common ancestry of eukaryotic endomembrane coatomers|journal=Scientific Reports|date=2 March 2016|volume=6|pages=22311|doi=10.1038/srep22311|pmid=26931514|pmc=4773986|bibcode=2016NatSR...622311P}}

Examination of the genome of Lokiarchaeum, thought to be among the closest archaeal relatives to eukaryotes, did not reveal any examples of the beta propeller/alpha solenoid domain architecture, although homologs of other proteins involved in eukaryotic membrane trafficking were identified. However, it is unclear whether this observation means that the propeller/solenoid architecture evolved later or was lost from modern lokiarchaea.{{cite journal|last1=Klinger|first1=Christen M.|last2=Spang|first2=Anja|last3=Dacks|first3=Joel B.|last4=Ettema|first4=Thijs J.G.|title=Tracing the Archaeal Origins of Eukaryotic Membrane-Trafficking System Building Blocks|journal=Molecular Biology and Evolution|date=June 2016|volume=33|issue=6|pages=1528–1541|doi=10.1093/molbev/msw034|pmid=26893300|doi-access=free}}

A survey of the sequenced genomes of complex prokaryotes from the PVC superphylum (Planctomycetota-Verrucomicrobiota-Chlamydiota) identified examples of proteins with homology to eukaryotic membrane trafficking proteins, including examples of the distinctive beta-propeller/alpha-solenoid domain architecture previously believed to be unique to eukaryotes. The PVC superphylum is known for containing bacteria with unusually complex membrane morphology, and this discovery has been cited as evidence in favor of these organisms' status as an intermediate form between prokaryotes and eukaryotes. The planctomycete Gemmata obscuriglobus has exceptionally complex membrane architecture and has been a source of controversy in the literature regarding the possibility that it has a membrane-bound "nucleoid" compartment enclosing its DNA.{{cite journal|last1=Fuerst|first1=John A.|title=Beyond Prokaryotes and Eukaryotes : Planctomycetes and Cell Organization|journal=Nature Education|date=2010|volume=3|issue=9|page=44}}{{cite journal|last1=McInerney|first1=JO|last2=Martin|first2=WF|last3=Koonin|first3=EV|last4=Allen|first4=JF|last5=Galperin|first5=MY|last6=Lane|first6=N|last7=Archibald|first7=JM|last8=Embley|first8=TM|title=Planctomycetes and eukaryotes: a case of analogy not homology.|journal=BioEssays|date=November 2011|volume=33|issue=11|pages=810–7|pmid=21858844|doi=10.1002/bies.201100045|pmc=3795523}}{{cite journal|last1=Fuerst|first1=JA|title=The PVC superphylum: exceptions to the bacterial definition?|journal=Antonie van Leeuwenhoek|date=October 2013|volume=104|issue=4|pages=451–66|pmid=23912444|doi=10.1007/s10482-013-9986-1|s2cid=14283647}}{{cite journal|last1=Devos|first1=Damien P.|title=Gemmata obscuriglobus|journal=Current Biology|date=September 2013|volume=23|issue=17|pages=R705–R707|doi=10.1016/j.cub.2013.07.013|pmid=24028944|doi-access=free}}{{cite journal|last1=Devos|first1=DP|title=Re-interpretation of the evidence for the PVC cell plan supports a Gram-negative origin.|journal=Antonie van Leeuwenhoek|date=February 2014|volume=105|issue=2|pages=271–4|pmid=24292377|doi=10.1007/s10482-013-0087-y|hdl=10261/129395|s2cid=16557669|hdl-access=free}}{{cite journal|last1=Devos|first1=Damien P.|title=PVC bacteria: variation of, but not exception to, the Gram-negative cell plan|journal=Trends in Microbiology|date=January 2014|volume=22|issue=1|pages=14–20|doi=10.1016/j.tim.2013.10.008|pmid=24286661|hdl=10261/129431|hdl-access=free}} The identification of proteins with sequence similarities to HEAT repeats in the G. obscuriglobus proteome has been interpreted as support for the membrane-bound nucleoid hypothesis;{{cite journal|last1=Fuerst|first1=John A.|last2=Sagulenko|first2=Evgeny|title=Towards understanding the molecular mechanism of the endocytosis-like process in the bacterium Gemmata obscuriglobus|journal=Biochimica et Biophysica Acta (BBA) - Molecular Cell Research|date=August 2014|volume=1843|issue=8|pages=1732–1738|doi=10.1016/j.bbamcr.2013.10.002|pmid=24144586|doi-access=free}} however, this has been disputed.

Low sequence similarity among alpha solenoid proteins of similar structure has impeded their identification using bioinformatics methods, since the repeats are often not well defined in sequence. A large number of different computational methods have been developed to identify candidate alpha solenoid proteins based on their amino acid sequence.{{cite journal|last1=Di Domenico|first1=Tomás|last2=Potenza|first2=Emilio|last3=Walsh|first3=Ian|last4=Gonzalo Parra|first4=R.|last5=Giollo|first5=Manuel|last6=Minervini|first6=Giovanni|last7=Piovesan|first7=Damiano|last8=Ihsan|first8=Awais|last9=Ferrari|first9=Carlo|last10=Kajava|first10=Andrey V.|last11=Tosatto|first11=Silvio C.E.|title=RepeatsDB: a database of tandem repeat protein structures|journal=Nucleic Acids Research|date=January 2014|volume=42|issue=D1|pages=D352–D357|doi=10.1093/nar/gkt1175|pmc=3964956|pmid=24311564}}{{cite journal|last1=Pellegrini|first1=Marco|title=Tandem Repeats in Proteins: Prediction Algorithms and Biological Role|journal=Frontiers in Bioengineering and Biotechnology|date=24 September 2015|volume=3|page=143|doi=10.3389/fbioe.2015.00143|pmc=4585158|pmid=26442257|doi-access=free}}

• [http://repeatsdb.bio.unipd.it/class/III.3 RepeatsDB] α-solenoid class

{{reflist|30em}}

{{Protein tandem repeats}}

Category:Protein folds