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The tetratricopeptide repeat (TPR) is a
structural motif In a polymer, chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common Biomolecular structure#Tertiary structure, three-dimensional structure that appears in a variety of different, evolutionarily unrel ...
. It consists of a
degenerate Degeneracy, degenerate, or degeneration may refer to: Arts and entertainment * Degenerate (album), ''Degenerate'' (album), a 2010 album by the British band Trigger the Bloodshed * Degenerate art, a term adopted in the 1920s by the Nazi Party i ...
34 amino acid
tandem repeat Tandem repeats occur in DNA when a pattern of one or more nucleotides is repeated and the repetitions are directly adjacent to each other. Several protein domains also form tandem repeats within their amino acid primary structure, such as armadil ...
identified in a wide variety of
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, respo ...
s. It is found in tandem arrays of 3–16 motifs, which form scaffolds to mediate protein–protein interactions and often the assembly of multiprotein complexes. These
alpha-helix 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 ear ...
pair repeats usually fold together to produce a single, linear solenoid domain called a TPR domain. Proteins with such domains include the
anaphase-promoting complex Anaphase-promoting complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins, including a culli ...
(APC) subunits
cdc16 Cell division cycle protein 16 homolog is a protein that in humans is encoded by the ''CDC16'' gene. Function This gene encodes a component protein of the APC complex, which is composed of eight proteins and functions as a protein ubiquitin li ...
,
cdc23 Cell division cycle 23 homolog (S. cerevisiae), also known as CDC23, is a protein that, in humans, is encoded by the ''CDC23'' gene. Function The CDC23 protein shares strong similarity with Saccharomyces cerevisiae Cdc23, a protein essential f ...
and
cdc27 Cell division cycle protein 27 homolog is a protein that in humans is encoded by the ''CDC27'' gene. Function The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae protein Cdc27, and the gene product of Schizo ...
, the
NADPH oxidase NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white ...
subunit p67-phox, hsp90-binding
immunophilin In molecular biology, immunophilins are endogenous cytosolic peptidyl-prolyl isomerases (PPI) that catalyze the interconversion between the cis and trans isomers of peptide bonds containing the amino acid proline (Pro). They are chaperone molecule ...
s,
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s, the
protein kinase R Protein kinase RNA-activated also known as protein kinase R (PKR), interferon-induced, double-stranded RNA-activated protein kinase, or eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) is an enzyme that in humans is encoded by t ...
(PKR), the major receptor for peroxisomal matrix protein import
PEX5 Peroxisomal targeting signal 1 receptor (PTS1R) is a protein that in humans is encoded by the ''PEX5'' gene. PTS1R is a peroxisomal targeting sequence involved in the specific transport of molecules for oxidation inside the peroxisome. SKL binds ...
, protein arginine methyltransferase 9 (PRMT9), and mitochondrial import proteins.


Structure

The structure of the PP5 protein was the first structure to be determined. The structure solved by
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
by Das and colleagues showed that the TPR sequence motif was composed of a pair of antiparallel alpha helices. The PP5 structure contained 3 tandem TPR repeats which showed the sequential TPR repeats formed an alpha-helical
solenoid upright=1.20, An illustration of a solenoid upright=1.20, Magnetic field created by a seven-loop solenoid (cross-sectional view) described using field lines A solenoid () is a type of electromagnet formed by a helix, helical coil of wire whose ...
structure. A typical TPR structure is characterized by interactions between helices A and B of the first motif and helix A’ of the next TPR. Although the nature of such interactions may vary, the first two helices of the TPR motif typically have a packing angle of ~24 degrees within a single motif. Repeats of more than three TPR motifs generate a right handed superhelix characterized by both a concave and a convex face, of which the concave face is usually involved in ligand binding. In terms of sequence, a TPR possesses a mixture of small and large hydrophobic residues, nonetheless, no positions are fully invariant. There are however certain residues that are usually conserved including Tryptophan 4, Leucine 7, Glycine 8, Tyrosine 11, Alanine 20, Phenylalanine 24, Alanine 27 and Proline 32. Among those 8, Alanine at positions 8, 20 and 27 tend to be more conserved. The other positions have a stronger preference for either small, large or aromatic amino acids rather than a specific residue. In between helices, residue conservation plays more of a structural role with helix breaking residues present. Between adjacent TPR, residues have roles with both structural and functional implications.


TPR containing peptides


Hop

The
Hop A hop is a type of jump. Hop or hops may also refer to: Arts and entertainment * ''Hop'' (film), a 2011 film * Hop! Channel, an Israeli TV channel * ''House of Payne'', or ''HOP'', an American sitcom * Lindy Hop, a swing dance of the 1920s and ...
adaptor protein mediates the association of the molecular chaperones Hsp70 and Hsp90. It contains three 3-TPR repeats each with its own peptide-binding specificity. Its TPR1 domain is known to recognize the C-terminal of Hsp70 while TPR2 binds to the C-terminal of Hsp90. Both C-terminal sequences end with an EEVD motif and the nature of the interaction is both electrostatic and hydrophobic.


PEX5

The
PEX5 Peroxisomal targeting signal 1 receptor (PTS1R) is a protein that in humans is encoded by the ''PEX5'' gene. PTS1R is a peroxisomal targeting sequence involved in the specific transport of molecules for oxidation inside the peroxisome. SKL binds ...
protein is a receptor for PTS1 (peroxisomal targeting signal tripeptide which directs proteins into peroxisomes). It interacts with the signal via TPR motifs. Most of its contacts with the C-terminal tripeptide PTS1 are in the concave face of TPRs 1, 2 and 3.


Neutrophil cytosolic factor 2

Neutrophil cytosolic factor 2 Neutrophil cytosol factor 2 is a protein that in humans is encoded by the ''NCF2'' gene. Function This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein complex known as NADPH oxidase found in ...
is an essential to NADPH oxidase complex which in turn produces superoxides in response to microbial infection. The binding of the Rac GTPase is a key step into the assembly of the complex and the TPRs in the phox unit mediate the assembly of the multiprotein complex by acting a binding scaffold.


Examples

Human genes encoding proteins containing this motif include: *
AAG2 AAG may refer to: * Ambrak language, a Torricelli language of Papua New Guinea * Assistant adjutant general, a military title * United States Assistant Attorney General, a ranking within the Department of Justice Business * American Advisors G ...
,
ANAPC7 Anaphase-promoting complex subunit 7 is an enzyme that in humans is encoded by the ''ANAPC7'' gene. Multiple transcript variants encoding different isoforms have been found for this gene. Function This gene encodes a tetratricopeptide repeat c ...
*
BBS4 Bardet–Biedl syndrome 4 is a protein that in humans is encoded by the ''BBS4'' gene. This gene encodes a protein which contains tetratricopeptide repeats (TPR), similar to O-linked N-acetylglucosamine transferase. Mutations in this gene have be ...
*
CABIN1 Calcineurin-binding protein cabin-1 is a protein that in humans is encoded by the ''CABIN1'' gene. Function Calcineurin plays an important role in the T-cell receptor-mediated signal transduction pathway. The protein encoded by this gene binds ...
,
CDC16 Cell division cycle protein 16 homolog is a protein that in humans is encoded by the ''CDC16'' gene. Function This gene encodes a component protein of the APC complex, which is composed of eight proteins and functions as a protein ubiquitin li ...
,
CDC23 Cell division cycle 23 homolog (S. cerevisiae), also known as CDC23, is a protein that, in humans, is encoded by the ''CDC23'' gene. Function The CDC23 protein shares strong similarity with Saccharomyces cerevisiae Cdc23, a protein essential f ...
,
CDC27 Cell division cycle protein 27 homolog is a protein that in humans is encoded by the ''CDC27'' gene. Function The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae protein Cdc27, and the gene product of Schizo ...
,
CNOT10 CCR4-NOT transcription complex subunit 10 is a protein that in humans is encoded by the CNOT10 gene. It is a subunit of the CCR4-Not Carbon Catabolite Repression—Negative On TATA-less, or CCR4-Not, is a multiprotein complex tha ...
,
CTR9 RNA polymerase-associated protein CTR9 homolog is an enzyme that in humans is encoded by the ''CTR9'' gene. Model organisms Model organisms have been used in the study of CTR9 function. A conditional knockout mouse line called ''Ctr9tm1b(EUCOMM)W ...
*
DNAJC3 DnaJ homolog subfamily C member 3 is a protein that in humans is encoded by the ''DNAJC3'' gene. Function The protein encoded by this gene contains multiple tetratricopeptide repeat (TPR) motifs as well as the highly conserved J domain found in ...
,
DNAJC7 DnaJ homolog subfamily C member 7 is a protein that in humans is encoded by the ''DNAJC7'' gene. Interactions DNAJC7 has been shown to interact with RAD9A Cell cycle checkpoint control protein RAD9A is a protein that in humans is encoded by t ...
,
DYX1C1 Dyslexia susceptibility 1 candidate gene 1 protein is a protein that in humans is encoded by the ''DYX1C1'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." ...
* FAM10A4, FAM10A5,
FKBP4 FK506-binding protein 4 is a protein that in humans is encoded by the ''FKBP4'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes i ...
,
FKBP5 FK506 binding protein 5, also known as FKBP5, is a protein which in humans is encoded by the ''FKBP5'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and ba ...
,
FKBP8 FK506-binding protein 8 is a protein that in humans is encoded by the ''FKBP8'' gene. The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving p ...
,
FKBPL FK506-binding protein like, also known as FKBPL, is a protein that in humans is encoded by the ''FKBPL'' gene. Function FKBPL has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes ...
* GPSM1,
GPSM2 G-protein-signaling modulator 2, also called LGN for its 10 Leucine-Glycine-Asparagine repeats, is a protein that in humans is encoded by the ''GPSM2'' gene. Function Heterotrimeric G proteins transduce extracellular signals received by cell s ...
, GTF3C3 *
IFIT1 Interferon-induced protein with tetratricopeptide repeats 1 is a protein that in humans is encoded by the ''IFIT1'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of her ...
, IFIT1L,
IFIT2 Interferon-induced protein with tetratricopeptide repeats 2 or IFIT2 is a protein found in humans which is encoded by the ''IFIT2'' gene. Clinical significance IFIT2 may play a role in prevention of tumor progression. Indeed, IFIT2 gene has b ...
, IFIT3, IFIT5,
IFT140 IFT140, Intraflagellar transport 140 homolog, is a protein that in humans is encoded by the ''IFT140'' gene. The gene product forms a core component of IFT-A complex which is indipensible for retrograde intraflagellar transport within the primary ...
,
IFT88 Intraflagellar transport protein 88 homolog is a protein that is encoded by the ''IFT88'' gene. Function This gene encodes a member of the tetratrico peptide repeat (TPR) family. Mutations of a similar gene in mouse can cause polycystic kidney ...
*
KLC1 Kinesin light chain 1 is a protein that in humans is encoded by the ''KLC1'' gene. Conventional kinesin is a tetrameric molecule composed of two heavy chains and two light chains, and transports various cargos along microtubules toward their plus ...
,
KLC2 Kinesin light chain 2 is a protein that in humans is encoded by the ''KLC2'' gene. Interactions KLC2 has been shown to interact with MAPK8IP3 and KIF5B. Model organisms Model organisms have been used in the study of KLC2 function. A conditi ...
,
KLC3 Kinesin light chain 3 is a protein that in humans is encoded by the ''KLC3'' gene. Function This gene encodes a member of the kinesin light chain gene family. Kinesins are molecular motors involved in the transport of cargo along microtubules, ...
,
KLC4 Kinesin light chain 4 is a protein that in humans is encoded by the ''KLC4'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''b ...
, KNS2 * LONRF2 * NARG1, NARG1L, NASP,
NCF2 Neutrophil cytosol factor 2 is a protein that in humans is encoded by the ''NCF2'' gene. Function This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein complex known as NADPH oxidase found in ...
, NFKBIL2, NOXA1,
NPHP3 Nephrocystin-3 is a protein that in humans is encoded by the ''NPHP3'' gene. This gene encodes a protein containing a coiled-coil (CC) domain, a tubulin-tyrosine ligase (TTL) domain, and a tetratrico peptide repeat (TPR) domain. The encoded protei ...
* OGT *
PEX5 Peroxisomal targeting signal 1 receptor (PTS1R) is a protein that in humans is encoded by the ''PEX5'' gene. PTS1R is a peroxisomal targeting sequence involved in the specific transport of molecules for oxidation inside the peroxisome. SKL binds ...
, PEX5L, PPID,
PPP5C Serine/threonine-protein phosphatase 5 is an enzyme that in humans is encoded by the ''PPP5C'' gene. Model organisms Model organisms have been used in the study of PPP5C function. A conditional knockout mouse line, called ''Ppp5ctm1a(EUCOMM) ...
,
PRPF6 Pre-mRNA-processing factor 6 is a protein that in humans is encoded by the ''PRPF6'' gene. The protein encoded by this gene appears to be involved in pre-mRNA splicing, possibly acting as a bridging factor between U5 and U4/U6 snRNPs in formation ...
*
RANBP2 RAN binding protein 2 (RANBP2) is protein which in humans is encoded by the ''RANBP2'' gene. It is also known as nucleoporin 358 (Nup358) since it is a member nucleoporin family that makes up the nuclear pore complex. RanBP2 has a mass of 358 kDa. ...
, RANBP2L2, RANBP2L6,
RAPSN 43 kDa receptor-associated protein of the synapse (rapsyn) is a protein that in humans is encoded by the ''RAPSN'' gene. Function This protein belongs to a family of proteins that are receptor associated proteins of the synapse. It contains a ...
,
RGPD5 RANBP2-like and GRIP domain-containing protein 5 is a protein that in humans is encoded by the ''RGPD5'' gene. RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a varie ...
, RGPD7, RPAP3 *
SGTA Small glutamine-rich tetratricopeptide repeat-containing protein alpha is a protein that in humans is encoded by the ''SGTA'' gene. ''SGTA'' orthologs have also been identified in several mammals for which complete genome data are available. Fu ...
, SGTB, SH3TC1, SH3TC2, SPAG1, SRP72,
ST13 Hsc70-interacting protein also known as suppression of tumorigenicity 13 (ST13) is a protein that in humans is encoded by the ''ST13'' gene. Function The protein encoded by this gene is an adaptor protein that mediates the association of the ...
,
STIP1 Hop, occasionally written HOP, is an abbreviation for Hsp70-Hsp90 Organizing Protein. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90. Hop belongs to the large group of co-chaperones, which r ...
,
STUB1 STUB1 (STIP1 homology and U-Box containing protein 1) is a human gene that codes for the protein CHIP (C terminus of HSC70-Interacting Protein). Function The CHIP protein encoded by this gene binds to and inhibits the ATPase activity of the cha ...
,
SUGT1 Suppressor of G2 allele of SKP1 homolog is a protein that in humans is encoded by the ''SUGT1'' gene. Function This gene is homologous to the yeast gene SGT1, which encodes a protein involved in kinetochore function and required for the G1/S an ...
* TMTC1, TMTC2, TMTC3, TMTC4,
TOMM34 Mitochondrial import receptor subunit TOM34 is a protein that in humans is encoded by the ''TOMM34'' gene. The protein encoded by this gene is involved in the import of precursor proteins into mitochondria. The encoded protein has a chaperone-lik ...
,
TOMM70A Mitochondrial import receptor subunit TOM70 is a protein that in humans is encoded by the ''TOMM70A'' gene. The translocase of outer mitochondrial membrane (TOM) complex is a multisubunit complex involved in the recognition, unfolding, and translo ...
*
TTC1 Tetratricopeptide repeat protein 1 is a protein that in humans is encoded by the ''TTC1'' gene. Interactions TTC1 has been shown to interact with HSPA4 Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the ''HSPA4'' gene. ...
,
TTC3 Tetratricopeptide repeat protein 3 is a protein that in humans is encoded by the ''TTC3'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''genera ...
,
TTC4 Tetratricopeptide repeat protein 4 is a protein that in humans is encoded by the ''TTC4'' gene. The 34-amino acid tetratricopeptide repeat The tetratricopeptide repeat (TPR) is a structural motif. It consists of a degenerate 34 amino acid tan ...
, TTC5, TTC6,
TTC7A Tetratricopeptide repeat domain 7A (TTC7A) is a protein that in humans is encoded by the ''TTC7A'' gene. Function TPR domain-containing proteins, such as TTC7A, have diverse functions in cell cycle control, protein transport, phosphate turnove ...
, TTC7B,
TTC8 Tetratricopeptide repeat domain 8 (TTC8) also known as Bardet–Biedl syndrome 8 is a protein that in humans is encoded by the ''TTC8'' gene. Function TTC8 is associated with gamma-tubulin, BBS4, and PCM1 in the centrosome. PCM1 in turn is in ...
, TTC9C,
TTC12 Tetratricopeptide repeat protein 1 is a protein that in humans is encoded by the ''TTC1'' gene. Interactions TTC1 has been shown to Protein-protein interaction, interact with HSPA4. References Further reading

* * * * * * * * {{gene-5 ...
, TTC13, TTC14, TTC15, TTC16, TTC17, TTC18, TTC21A, TTC21B, TTC22, TTC24, TTC25, TTC27, TTC28,
TTC29 TTC may refer to: In arts and entertainment * Tao Te Ching, the collection of sayings attributed to Lao Tzu * Tom Tom Club, an American new wave band * The Travel Channel, a cable channel devoted to travel * The Tennis Channel, a digital channel ...
, TTC30A, TTC30B, TTC31, TTC33, TTC37 * UNC45A, UNC45B, UTX, UTY * WDTC1 * ZC3H7B


References


Further reading

* * * * * * * *


External links

* * {{Protein tandem repeats TPR domain