An alpha solenoid (sometimes also known as an alpha horseshoe or as stacked pairs of alpha helices, abbreviated SPAH) is a protein fold composed of repeating alpha helix subunits, commonly helix-turn-helix motifs, arranged in antiparallel fashion to form a superhelix. Alpha solenoids are known for their flexibility and plasticity. Like beta propellers, alpha solenoids are a form of solenoid protein domain commonly found in the proteins comprising the nuclear pore complex. They are also common in membrane coat proteins known as coatomers, such as clathrin, and in regulatory proteins that form extensive protein-protein interactions with their binding partners. Examples of alpha solenoid structures binding RNA and lipids have also been described.

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. 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" 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. This latter domain architecture also occurs in clathrin and Sec31, and was thought to be unique to eukaryotes, though a few examples have been reported in planctomycetes.

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.

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. Transporters of other molecules, such as RNA, can also be of alpha solenoid architecture, as in exportin-5 or pentatricopeptide-repeat-containing RNA-binding proteins, which are particularly common in plants.