GroES
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Heat shock 10 kDa protein 1 (Hsp10), also known as chaperonin 10 (cpn10) or early-pregnancy factor (EPF), is a
protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one location to another. Proteins differ from one another primarily ...

protein
that in humans is encoded by the ''HSPE1''
gene In biology, a gene (from ''genos'' "...Wilhelm Johannsen coined the word gene to describe the Mendelian_inheritance#History, Mendelian units of heredity..." (Greek language, Greek) meaning ''generation'' or ''birth'' ) is a basic unit of her ...

gene
. The homolog in ''
E. coli
E. coli
'' is GroES that is a
chaperonin 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 bel ...
which usually works in conjunction with
GroEL GroEL is a protein which belongs to the chaperonin family of Chaperone (protein), molecular chaperones, and is found in many bacteria. It is required for the proper protein folding, folding of many proteins. To function properly, GroEL requires th ...

GroEL
.


Structure and function

GroES exists as a ring-shaped
oligomer In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they underg ...
of between six and eight identical subunits, while the 60 kDa chaperonin (cpn60 - or groEL in bacteria) forms a
structure A structure is an arrangement and organization of interrelated elements in a material object or system A system is a group of Interaction, interacting or interrelated elements that act according to a set of rules to form a unified whole. A ...

structure
comprising 2 stacked rings, each ring containing 7 identical subunits. 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 Protein folding is the physical process by which a protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of func ...

protein folding
whilst cpn-10
bind BIND (), or named (pronounced ''name-dee'': , short for ''name daemon Daemon is the Latin word for the Ancient Greek daimon (δαίμων: "god", "godlike", "power", "fate"), which originally referred to a lesser deity or guiding spirit such a ...
s to cpn-60 and synchronizes the release of the
folded
folded
protein in an Mg2+-ATP dependent manner. The binding of cpn10 to cpn60 inhibits the weak ATPase activity of cpn60. ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative Gram-negative bacteria are bacteria that do not retain the crystal violet st ...

Escherichia coli
'' GroES has also been shown to bind
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals * American Technical Publishers * ', a Danish pension * Armenia Tree Project * Association for Transpersonal Psychology * ATP architects engineers office * ATP ...

ATP
cooperatively, and with an affinity comparable to that of GroEL. Each GroEL subunit contains three
structurally A structure is an arrangement and organization of interrelated elements in a material object or system A system is a group of Interaction, interacting or interrelated elements that act according to a set of rules to form a unified whole. A sy ...
distinct domains: an apical, an intermediate and an equatorial domain. The apical domain contains the
binding site Binding may refer to: Computing * Binding, associating a network socket with a local port number and IP address * Data binding, the technique of connecting two data elements together ** UI data binding, linking a user interface element to an ele ...
s 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 300px, Allosteric regulation of an enzyme In biochemistry Biochemistry or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be ...

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 Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution Substitution may refer to: Arts and media *Chord substitution, in music, swapping one chord for ...

hydrolysis
for substrate protein release.


Interactions

GroES has been shown to
interact Interact may refer to: * Interaction Interaction is a kind of action that occurs as two or more objects have an effect upon one another. The idea of a two-way effect is essential in the concept of interaction, as opposed to a one-way causal ef ...
with
GroEL GroEL is a protein which belongs to the chaperonin family of Chaperone (protein), molecular chaperones, and is found in many bacteria. It is required for the proper protein folding, folding of many proteins. To function properly, GroEL requires th ...

GroEL
.


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 cervix, cervical mucus and in amniotic fluid. EPF may be detected in sheep within 72 hours of mating, in mice within 24 hours of mating, and in samples from media surrounding human embryos fertilized in vitro within 48 hours of fertilization (although another study failed to duplicate this finding for ''in vitro'' embryos). EPF has been detected as soon as within six hours of mating. 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. 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. However, progress in characterization of EPF has been made and its existence is well-accepted in the scientific community.


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. After implantation, EPF may be produced by the conceptus directly. 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. Injecting anti-EPF antibodies into mice after mating significantly reduced the number of successful pregnancies and number of pups; no effect on growth was seen when mice embryos were cultured in media containing anti-EPF antibodies. While some actions of EPF are the same in all mammals (namely rosette inhibition), other immunosuppressant mechanism vary between species. In mice, EPF levels are high in early pregnancy, but on day 15 decline to levels found in non-pregnant mice. In humans, EPF levels are high for about the first twenty weeks, then decline, becoming undetectable within eight weeks of childbirth, delivery.


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. Interest in EPF for this purpose has continued, although current test methods have not proved sufficiently accurate for the requirements of livestock management. 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. 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. The accuracy of EPF as a pregnancy test in humans has been found to be high by several studies.


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 Intrauterine device, IUDs concluded that post-fertilization mechanisms contribute significantly to the effectiveness of these devices. 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. For groups that define beginning of pregnancy controversy, 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.


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 Spontaneous abortion, lost within ten days of ovulation (43% rate of early conceptus loss). Use of EPF has been proposed to distinguish infertility caused by failure to conceive versus infertility caused by failure to implant. 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.


As a tumour marker

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


References


Further reading

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External links

*
3D macromolecular structures of GroES in EMDB
{{InterPro content, IPR020818 Protein domains Protein complexes Tests for pregnancy Moonlighting proteins Co-chaperones