Importin is a type of

karyopherin Karyopherins are proteins involved in transporting molecules between the cytoplasm and the nucleus of a eukaryotic cell. The inside of the nucleus is called the karyoplasm (or nucleoplasm). Generally, karyopherin-mediated transport occurs through ...

that transports

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

molecules from the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

to the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...

. It does so by binding to specific

recognition sequence A recognition sequence is a DNA sequence to which a structural motif of a DNA-binding domain exhibits binding specificity. Recognition sequences are palindromes. The transcription factor Sp1 for example, binds the sequences 5'-(G/T)GGGCGG(G/A)(G ...

s, called

nuclear localization sequence A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines ...

s (NLS). Importin has two subunits, importin α and importin β. Members of the importin-β family can bind and transport cargo by themselves, or can form

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

s with importin-α. As part of a

, importin-β mediates interactions with the pore complex, while importin-α acts as an adaptor protein to bind the

nuclear localization signal A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysine ...

(NLS) on the cargo. The NLS-Importin α-Importin β trimer dissociates after binding to

Ran Ran, RaN and ran may refer to: Arts and entertainment * ''Ran'' (film), a 1985 film directed by Akira Kurosawa * "Ran" (song), a 2013 Japanese song by Luna Sea * ''Ran Online'', a 2004 MMORPG (massively multiplayer online role playing game) *' ...

GTP inside the

, with the two importin proteins being recycled to the

for further use.

Discovery

Importin can exist as either a

of importin-α/β or as a

monomer In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification ...

of Importin-β. Importin-α was first isolated in 1994 by a group includin
Enno Hartmann
based at the

Max Delbrück Center for Molecular Medicine Max or MAX may refer to: Animals * Max (dog) (1983–2013), at one time purported to be the world's oldest living dog * Max (English Springer Spaniel), the first pet dog to win the PDSA Order of Merit (animal equivalent of OBE) * Max (gorilla) (1 ...

. The process of nuclear protein import had already been characterised in previous reviews, but the key proteins involved had not been elucidated up until that point. A 60 kDa

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

ic protein, essential for protein import into the nucleus, and with a 44%

sequence identity In bioinformatics, a sequence alignment is a way of arranging the sequences of DNA, RNA, or protein to identify regions of similarity that may be a consequence of functional, structural, or evolutionary relationships between the sequences. Alig ...

t
SRP1p
was purified from ''

Xenopus ''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-kno ...

'' eggs. It was cloned, sequenced and expressed in ''

E.coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'' and in order to completely reconstitute signal dependent transport, had to be combined with

(TC4). Other key stimulatory factors were also found in the study. Importin-β, unlike importin-α, has no direct homologues in yeast, but was purified as a 90-95 kDa protein and found to form a

with importin-α in a number of different cases. These included a study led by Michael Rexach and further studies b
Dirk Görlich
These groups found that importin-α requires another protein, importin-β to function, and that together they form a receptor for nuclear localization signals (NLS), thus allowing transport into the

. Since these initial discoveries in 1994 and 1995, a host of Importin genes, such as

IPO4 Importin-4 is a protein that in humans is encoded by the ''IPO4'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or '' ...

and

IPO7 Importin-7 is a protein that in humans is encoded by the ''IPO7'' gene. The importin-alpha/beta complex and the GTPase Ran mediate nuclear import of proteins with a classical nuclear localization signal. The protein encoded by this gene is a membe ...

, have been found that facilitate the import of slightly different cargo proteins, due to their differing structure and locality.

Structure

Importin-α

A large proportion of the importin-α adaptor protein is made up of several armadillo repeats (ARM) arranged in

tandem Tandem, or in tandem, is an arrangement in which a team of machines, animals or people are lined up one behind another, all facing in the same direction. The original use of the term in English was in ''tandem harness'', which is used for two ...

. These repeats can stack together to form a curved shaped structure, which facilitates binding to the NLS of specific cargo proteins. The major NLS binding site is found towards the

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

, with a minor site being found at the

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein i ...

. As well as the

ARM In human anatomy, the arm refers to the upper limb in common usage, although academically the term specifically means the upper arm between the glenohumeral joint (shoulder joint) and the elbow joint. The distal part of the upper limb between t ...

structures, Importin-α also contains a 90

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

region, responsible for binding to Importin-β, known as the Importin-β binding (IBB)domain. This is also a site of autoinhibition, and is implicated in the release of cargo once importin-α reaches the

Importin-β

Importin-β is the typical structure of a larger

superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilies. Domains are functional, str ...

s. The basis of their structure is 18-20 tandem repeats of the

HEAT In thermodynamics, heat is defined as the form of energy crossing the boundary of a thermodynamic system by virtue of a temperature difference across the boundary. A thermodynamic system does not ''contain'' heat. Nevertheless, the term is ...

motif. Each one of these repeats contains two antiparallel

alpha helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earli ...

linked by a

turn Turn may refer to: Arts and entertainment Dance and sports * Turn (dance and gymnastics), rotation of the body * Turn (swimming), reversing direction at the end of a pool * Turn (professional wrestling), a transition between face and heel * Turn, ...

, which stack together