The term "alpha solenoid" has been used somewhat inconsistently in the literature.[4] As originally defined, alpha solenoids were composed of
helix-turn-helix motifs that stacked into an open superhelix.[5] 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" [6] for these proteins, and uses "alpha solenoid" for a somewhat different and more compact structure exemplified by the
peridinin-chlorophyll binding protein.[4]
Alpha solenoids have unusual elasticity and flexibility relative to
globular proteins.[2][3] 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.[5] 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.[2]
Because they are composed of repeating relatively short subunits, alpha solenoids can acquire additional subunits relatively easily, resulting in new interaction surface properties.[2] As a result, known alpha solenoid proteins vary substantially in length.[4]
Function
Nuclear pore complex components
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.[4] 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.[7][8] This latter domain architecture also occurs in
clathrin and
Sec31, and was thought to be unique to
eukaryotes,[7][9] though a few examples have been reported in
planctomycetes.[10]
Vesicle coat proteins
Vesicle coat proteins frequently contain alpha solenoids and share common domain architecture with some NPC proteins.[7] 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.[12]
Transport proteins
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.[2] 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.[13] Transporters of other molecules, such as
RNA, can also be of alpha solenoid architecture, as in
exportin-5[14] or
pentatricopeptide-repeat-containing RNA-binding proteins, which are particularly common in plants.[15][16]
Regulatory proteins
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.[18][1]
Taxonomic distribution
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.[2]
Evolution
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.[2]
Nuclear pore complexes and vesicle transport
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.[7][8] An ancestral "protocoatomer" that diversified to acquire derived characteristics of all four modern complexes has been proposed.[4][19][20][21]
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.[22]
Membrane coat proteins in prokaryotes
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.[10] 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.[23][24][25][26][27][28] The identification of proteins with sequence similarities to HEAT repeats in the G. obscuriglobusproteome has been interpreted as support for the membrane-bound nucleoid hypothesis;[29] however, this has been disputed.[24]
Bioinformatics
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.[2][30][31]
^
abcKobe, Bostjan; Kajava, Andrey V (October 2000). "When protein folding is simplified to protein coiling: the continuum of solenoid protein structures". Trends in Biochemical Sciences. 25 (10): 509–515.
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^Ybe, Joel A.; Brodsky, Frances M.; Hofmann, Kay; Lin, Kai; Liu, Shu-Hui; Chen, Lin; Earnest, Thomas N.; Fletterick, Robert J.; Hwang, Peter K. (27 May 1999). "Clathrin self-assembly is mediated by a tandemly repeated superhelix". Nature. 399 (6734): 371–375.
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^Field, Mark C; Dacks, Joel B (February 2009). "First and last ancestors: reconstructing evolution of the endomembrane system with ESCRTs, vesicle coat proteins, and nuclear pore complexes". Current Opinion in Cell Biology. 21 (1): 4–13.
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