GroES

Last updated
HSPE1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HSPE1 , heat shock 10kDa protein 1, CPN10, EPF, GROES, HSP10, heat shock protein family E (Hsp10) member 1
External IDs OMIM: 600141 MGI: 104680 HomoloGene: 20500 GeneCards: HSPE1
Orthologs
SpeciesHumanMouse
Entrez

3336

15528

Ensembl

ENSG00000115541

ENSMUSG00000073676

UniProt

P61604

Q64433

RefSeq (mRNA)

NM_002157

NM_008303

RefSeq (protein)

NP_002148

NP_032329

Location (UCSC) Chr 2: 197.5 – 197.5 Mb Chr 1: 55.13 – 55.13 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Cpn10
PDB 1g31 EBI.jpg
gp31 co-chaperonin from bacteriophage t4
Identifiers
SymbolCpn10
Pfam PF00166
Pfam clan CL0296
InterPro IPR020818
PROSITE PDOC00576
SCOP2 1lep / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

Heat shock 10 kDa protein 1 (Hsp10), also known as chaperonin 10 (cpn10) or early-pregnancy factor (EPF), is a protein that in humans is encoded by the HSPE1 gene. The homolog in E. coli is GroES that is a chaperonin which usually works in conjunction with GroEL. [5]

Contents

Structure and function

GroES exists as a ring-shaped oligomer of between six and eight identical subunits, while the 60 kDa chaperonin (cpn60, or groEL in bacteria) forms a structure comprising 2 stacked rings, each ring containing 7 identical subunits. [6] These ring structures assemble by self-stimulation in the presence of Mg2+-ATP. The central cavity of the cylindrical cpn60 tetradecamer provides an isolated environment for protein folding whilst cpn-10 binds to cpn-60 and synchronizes the release of the folded protein in an Mg2+-ATP dependent manner. [7] The binding of cpn10 to cpn60 inhibits the weak ATPase activity of cpn60.

Escherichia coli GroES has also been shown to bind ATP cooperatively, and with an affinity comparable to that of GroEL. [8] Each GroEL subunit contains three structurally distinct domains: an apical, an intermediate and an equatorial domain. The apical domain contains the binding sites for both GroES and the unfolded protein substrate. The equatorial domain contains the ATP-binding site and most of the oligomeric contacts. The intermediate domain links the apical and equatorial domains and transfers allosteric information between them. The GroEL oligomer is a tetradecamer, cylindrically shaped, that is organised in two heptameric rings stacked back to back. Each GroEL ring contains a central cavity, known as the `Anfinsen cage', that provides an isolated environment for protein folding. The identical 10 kDa subunits of GroES form a dome-like heptameric oligomer in solution. ATP binding to GroES may be important in charging the seven subunits of the interacting GroEL ring with ATP, to facilitate cooperative ATP binding and hydrolysis for substrate protein release.

Interactions

GroES has been shown to interact with GroEL. [9] [10]

Detection

Early pregnancy factor is tested for rosette inhibition assay. EPF is present in the maternal serum (blood plasma) shortly after fertilization; EPF is also present in cervical mucus [11] and in amniotic fluid. [12]

EPF may be detected in sheep within 72 hours of mating, [13] in mice within 24 hours of mating, [14] and in samples from media surrounding human embryos fertilized in vitro within 48 hours of fertilization [15] (although another study failed to duplicate this finding for in vitro embryos). [16] EPF has been detected as soon as within six hours of mating. [17]

Because the rosette inhibition assay for EPF is indirect, substances that have similar effects may confound the test. Pig semen, like EPF, has been shown to inhibit rosette formation – the rosette inhibition test was positive for one day in sows mated with a vasectomized boar, but not in sows similarly stimulated without semen exposure. [18] A number of studies in the years after the discovery of EPF were unable to reproduce the consistent detection of EPF in post-conception females, and the validity of the discovery experiments was questioned. [19] However, progress in characterization of EPF has been made and its existence is well-accepted in the scientific community. [20] [21]

Origin

Early embryos are not believed to directly produce EPF. Rather, embryos are believed to produce some other chemical that induces the maternal system to create EPF. [22] [23] [24] [25] [26] After implantation, EPF may be produced by the conceptus directly. [16]

EPF is an immunosuppressant. Along with other substances associated with early embryos, EPF is believed to play a role in preventing the immune system of the pregnant female from attacking the embryo. [17] [27] Injecting anti-EPF antibodies into mice after mating significantly [ quantify ] reduced the number of successful pregnancies and number of pups; [28] [29] no effect on growth was seen when mice embryos were cultured in media containing anti-EPF antibodies. [30] While some actions of EPF are the same in all mammals (namely rosette inhibition), other immunosuppressant mechanism vary between species. [31]

In mice, EPF levels are high in early pregnancy, but on day 15 decline to levels found in non-pregnant mice. [32] In humans, EPF levels are high for about the first twenty weeks, then decline, becoming undetectable within eight weeks of delivery. [33] [34]

Clinical utility

Pregnancy testing

It has been suggested that EPF could be used as a marker for a very early pregnancy test, and as a way to monitor the viability of ongoing pregnancies in livestock. [13] Interest in EPF for this purpose has continued, [35] although current test methods have not proved sufficiently accurate for the requirements of livestock management. [36] [37] [38] [39]

In humans, modern pregnancy tests detect human chorionic gonadotropin (hCG). hCG is not present until after implantation, which occurs six to twelve days after fertilization. [40] In contrast, EPF is present within hours of fertilization. While several other pre-implantation signals have been identified, EPF is believed to be the earliest possible marker of pregnancy. [14] [41] The accuracy of EPF as a pregnancy test in humans has been found to be high by several studies. [42] [43] [44] [45]

Birth control research

EPF may also be used to determine whether pregnancy prevention mechanism of birth control methods act before or after fertilization. A 1982 study evaluating EPF levels in women with IUDs concluded that post-fertilization mechanisms contribute significantly[ quantify ] to the effectiveness of these devices. [46] However, more recent evidence, such as tubal flushing studies indicates that IUDs work by inhibiting fertilization, acting earlier in the reproductive process than previously thought. [47]

For groups that define pregnancy as beginning with fertilization, birth control methods that have postfertilization mechanisms are regarded as abortifacient. There is currently contention over whether hormonal contraception methods have post-fertilization methods, specifically the most popular hormonal method: the combined oral contraceptive pill (COCP). The group Pharmacists for Life has called for a large-scale clinical trial to evaluate EPF in women taking COCPs; this would be the most conclusive evidence available to determine whether COCPs have postfertilization mechanisms. [48]

Infertility and early pregnancy loss

EPF is useful when investigating embryo loss prior to implantation. One study in healthy human women seeking pregnancy detected fourteen pregnancies with EPF. Of these, six were lost within ten days of ovulation (43% rate of early conceptus loss). [49]

Use of EPF has been proposed to distinguish infertility caused by failure to conceive versus infertility caused by failure to implant. [50] EPF has also been proposed as a marker of viable pregnancy, more useful in distinguishing ectopic or other nonviable pregnancies than other chemical markers such as hCG and progesterone. [51] [52] [53] [54]

As a tumour marker

Although almost exclusively associated with pregnancy, EPF-like activity has also been detected in tumors of germ cell origin [55] [56] and in other types of tumors. [57] Its utility as a tumour marker, to evaluate the success of surgical treatment, has been suggested. [58]

Related Research Articles

<span class="mw-page-title-main">Endometrium</span> Inner mucous membrane of the mammalian uterus

The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer thickens and then is shed during menstruation in humans and some other mammals, including apes, Old World monkeys, some species of bat, the elephant shrew and the Cairo spiny mouse. In most other mammals, the endometrium is reabsorbed in the estrous cycle. During pregnancy, the glands and blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus. The speculated presence of an endometrial microbiota has been argued against.

<span class="mw-page-title-main">Ectopic pregnancy</span> Female reproductive system health issue

Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms. The pain may be described as sharp, dull, or crampy. Pain may also spread to the shoulder if bleeding into the abdomen has occurred. Severe bleeding may result in a fast heart rate, fainting, or shock. With very rare exceptions, the fetus is unable to survive.

<span class="mw-page-title-main">In vitro fertilisation</span> Assisted reproductive technology procedure

In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro. The process involves monitoring and stimulating a woman's ovulatory process, removing an ovum or ova from their ovaries and letting a man's sperm fertilise them in a culture medium in a laboratory. After the fertilised egg (zygote) undergoes embryo culture for 2–6 days, it is transferred by catheter into the uterus, with the intention of establishing a successful pregnancy.

<span class="mw-page-title-main">Assisted reproductive technology</span> Methods to achieve pregnancy by artificial or partially artificial means

Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes or embryos, and/or the use of fertility medication. When used to address infertility, ART may also be referred to as fertility treatment. ART mainly belongs to the field of reproductive endocrinology and infertility. Some forms of ART may be used with regard to fertile couples for genetic purpose. ART may also be used in surrogacy arrangements, although not all surrogacy arrangements involve ART. The existence of sterility will not always require ART to be the first option to consider, as there are occasions when its cause is a mild disorder that can be solved with more conventional treatments or with behaviors based on promoting health and reproductive habits.

<span class="mw-page-title-main">Embryo transfer</span> Method of assisted reproduction

Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique - which is often used in connection with in vitro fertilization (IVF) - may be used in humans or in other animals, in which situations and goals may vary.

<span class="mw-page-title-main">GroEL</span> Protein-coding gene in the species Homo sapiens

GroEL is a protein which belongs to the chaperonin family of molecular chaperones, and is found in many bacteria. It is required for the proper folding of many proteins. To function properly, GroEL requires the lid-like cochaperonin protein complex GroES. In eukaryotes the organellar proteins Hsp60 and Hsp10 are structurally and functionally nearly identical to GroEL and GroES, respectively, due to their endosymbiotic origin.

<span class="mw-page-title-main">Chaperonin</span> InterPro Family

HSP60, also known as chaperonins (Cpn), is a family of heat shock proteins originally sorted by their 60kDa molecular mass. They prevent misfolding of proteins during stressful situations such as high heat, by assisting protein folding. HSP60 belong to a large class of molecules that assist protein folding, called molecular chaperones.

<span class="mw-page-title-main">Implantation (embryology)</span> First stage of pregnancy

Implantation, also known as nidation, is the stage in the embryonic development of mammals in which the blastocyst hatches, attaches, adheres, and invades into the wall of the female's uterus. Implantation is the first stage of gestation, and, when successful, the female is considered to be pregnant. An implanted embryo is detected by the presence of increased levels of human chorionic gonadotropin (hCG) in a pregnancy test. The implanted embryo will receive oxygen and nutrients in order to grow.

<span class="mw-page-title-main">Oocyte cryopreservation</span> Procedure to preserve a womans eggs (oocytes)

Oocyte cryopreservation is a procedure to preserve a woman's eggs (oocytes). This technique has been used to postpone pregnancy. When pregnancy is desired, the eggs can be thawed, fertilized, and transferred to the uterus as embryos. Several studies have shown that most infertility problems are due to germ cell deterioration related to aging. The procedure's success rate varies depending on the age of the woman, with the odds being higher in younger, adult women.

Transvaginal oocyte retrieval (TVOR), also referred to as oocyte retrieval (OCR), is a technique used in in vitro fertilization (IVF) in order to remove oocytes from the ovary of a woman, enabling fertilization outside the body. Transvaginal oocyte retrieval is more properly referred to as transvaginal ovum retrieval when the oocytes have matured into ova, as is normally the case in IVF. It can be also performed for egg donation, oocyte cryopreservation and other assisted reproduction technology such as ICSI.

Immunocontraception is the use of an animal's immune system to prevent it from fertilizing offspring. Contraceptives of this type are not currently approved for human use.

<span class="mw-page-title-main">Glycodelin</span> Mammalian protein found in Homo sapiens

Glycodelin(GD) also known as human placental protein-14 (PP-14)progestogen-associated endometrial protein (PAEP) or pregnancy-associated endometrial alpha-2 globulin is a glycoprotein that inhibits cell immune function and plays an essential role in the pregnancy process. In humans is encoded by the PAEP gene.

Reproductive immunology refers to a field of medicine that studies interactions between the immune system and components related to the reproductive system, such as maternal immune tolerance towards the fetus, or immunological interactions across the blood-testis barrier. The concept has been used by fertility clinics to explain fertility problems, recurrent miscarriages and pregnancy complications observed when this state of immunological tolerance is not successfully achieved. Immunological therapy is a method for treating many cases of previously "unexplained infertility" or recurrent miscarriage.

Jacques Cohen is a Dutch embryologist based in New York, U.S. He is currently Director at Reprogenetics LLC, Laboratory Director at ART Institute of Washington at Walter Reed National Military Medical Center, and Scientific Director of R & D at IVF-online.

Embryo quality is the ability of an embryo to perform successfully in terms of conferring a high pregnancy rate and/or resulting in a healthy person. Embryo profiling is the estimation of embryo quality by qualification and/or quantification of various parameters. Estimations of embryo quality guides the choice in embryo selection in in vitro fertilization.

Endometriosis and its complications are a major cause of female infertility. Endometriosis is a dysfunction characterized by the migration of endometrial tissue to areas outside of the endometrium of the uterus. The most common places to find stray tissue are on ovaries and fallopian tubes, followed by other organs in the lower abdominal cavity such as the bladder and intestines. Typically, the endometrial tissue adheres to the exteriors of the organs, and then creates attachments of scar tissue called adhesions that can join adjacent organs together. The endometrial tissue and the adhesions can block a fallopian tube and prevent the meeting of ovum and sperm cells, or otherwise interfere with fertilization, implantation and, rarely, the carrying of the fetus to term.

<span class="mw-page-title-main">Uterine microbiome</span>

The uterine microbiome is the commensal, nonpathogenic, bacteria, viruses, yeasts/fungi present in a healthy uterus, amniotic fluid and endometrium and the specific environment which they inhabit. It has been only recently confirmed that the uterus and its tissues are not sterile. Due to improved 16S rRNA gene sequencing techniques, detection of bacteria that are present in low numbers is possible. Using this procedure that allows the detection of bacteria that cannot be cultured outside the body, studies of microbiota present in the uterus are expected to increase.

Norbert Gleicher is an American obstetrician-gynecologist active in obstetrical practice, in vitro fertilization, reproductive endocrinology, and reproductive immunology. He is a fellow of the American College of Obstetricians and Gynecologists (FACOG) and the American College of Surgeons (ACS) and currently serves as president, medical director and chief scientist of the Center for Human Reproduction (CHR) in New York City, a clinical fertility center that he founded in 1981. Simultaneously, he is President of the Foundation for Reproductive Medicine, a not-for-profit research foundation. Gleicher maintains additional academic appointments at Rockefeller University, and Medical University of Vienna.

<span class="mw-page-title-main">Preimplantation factor</span> Peptide involved in placental development

Preimplantation factor(PIF) is a peptide secreted by trophoblast cells prior to placenta formation in early embryonic development. Human embryos begin to express PIF at the 4-cell stage, with expression increasing by the morula stage and continuing to do so throughout the first trimester. Expression of preimplantation factor in the blastocyst was discovered as an early correlate of the viability of the eventual pregnancy. Preimplantation factor was identified in 1994 by a lymphocyte platelet-binding assay, where it was thought to be an early biomarker of pregnancy. It has a simple primary structure with a short sequence of fifteen amino acids without any known quaternary structure. A synthetic analogue of preimplantation factor (commonly abbreviated in studies as sPIF or PIF*) that has an identical amino acid sequence and mimics the normal biological activity of PIF has been developed and is commonly used in research studies, particularly those that aim to study potential adult therapeutics.

<span class="mw-page-title-main">Use of assisted reproductive technology by LGBT people</span>

Lesbian, gay, bisexual, and transgender people people wishing to have children may use assisted reproductive technology. In recent decades, developmental biologists have been researching and developing techniques to facilitate same-sex reproduction.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000115541 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000073676 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: HSPE1 heat shock 10kDa protein 1 (chaperonin 10)".
  6. ↑ Hemmingsen SM, Woolford C, van der Vies SM, Tilly K, Dennis DT, Georgopoulos CP, Hendrix RW, Ellis RJ (May 1988). "Homologous plant and bacterial proteins chaperone oligomeric protein assembly". Nature. 333 (6171): 330–4. Bibcode:1988Natur.333..330H. doi:10.1038/333330a0. PMID   2897629. S2CID   4325057.
  7. ↑ Schmidt A, Schiesswohl M, Völker U, Hecker M, Schumann W (June 1992). "Cloning, sequencing, mapping, and transcriptional analysis of the groESL operon from Bacillus subtilis". J. Bacteriol. 174 (12): 3993–9. doi:10.1128/jb.174.12.3993-3999.1992. PMC   206108 . PMID   1350777.
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  37. ↑ Sasser RG, Ruder CA (1987). "Detection of early pregnancy in domestic ruminants". Journal of Reproduction and Fertility. Supplement. 34: 261–71. PMID   3305923.
  38. ↑ Gandy B, Tucker W, Ryan P, Williams A, Tucker A, Moore A, Godfrey R, Willard S (Sep 2001). "Evaluation of the early conception factor (ECF) test for the detection of nonpregnancy in dairy cattle". Theriogenology. 56 (4): 637–47. doi:10.1016/S0093-691X(01)00595-7. PMID   11572444.
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  40. ↑ Wilcox AJ, Baird DD, Weinberg CR (Jun 1999). "Time of implantation of the conceptus and loss of pregnancy". The New England Journal of Medicine. 340 (23): 1796–9. doi: 10.1056/NEJM199906103402304 . PMID   10362823.
  41. ↑ Straube W (1989). "[Early embryonal signals]". Zentralblatt für Gynäkologie. 111 (10): 629–33. PMID   2665388.
  42. ↑ Smart YC, Roberts TK, Fraser IS, Cripps AW, Clancy RL (Jun 1982). "Validation of the rosette inhibition test for the detection of early pregnancy in women". Fertility and Sterility. 37 (6): 779–85. doi: 10.1016/S0015-0282(16)46338-7 . PMID   6177559.
  43. ↑ Bessho T, Taira S, Ikuma K, Shigeta M, Koyama K, Isojima S (Mar 1984). "[Detection of early pregnancy factor in the sera of conceived women before nidation]". Nihon Sanka Fujinka Gakkai Zasshi. 36 (3): 391–6. PMID   6715922.
  44. ↑ Straube W, Tiemann U, Loh M, Schütz M (1989). "Detection of early pregnancy factor (EPF) in pregnant and nonpregnant subjects with the rosette inhibition test". Archives of Gynecology and Obstetrics. 246 (3): 181–7. doi:10.1007/BF00934079. PMID   2619332. S2CID   20531983.
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