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Retroelement integrases (INTs) are zinc finger nucleic acid-processing enzymes that catalyze the insertion of reverse-transcribed retroviral DNA into the host genome ([[literature:13067|Chiu and Davies 2004]]; [[literature:100803|Nowotny 2009]]). These enzymes remove two bases from the end of the LTR and are responsible for the insertion of the linear double-stranded viral DNA copy into the host cell DNA. INT amino acid architecture includes three subdomains:

* The N-terminal subdomain, which displays a conserved Zinc finger "HHCC" binding motif ([[literature:44689|Lodi ''et al''. 1995]]).
* The central subdomain, which contains a catalytic core characterized by the presence of a conserved D-D-E motif ([[literature:37555|Kan ''et al''. 1991]]; [[literature:60213|Polard and Chandler 1995]]).
* The C-terminal subdomain, which is less preserved than the others.

This enzyme seems to be related to unspecific DNA-binding although several studies of chimeric integrases assign this function to the central core ([[literature:36821|Katzman and Sudol 1995]]; [[literature:69203|Shibagaki and Chow 1997]]), while other authors alternatively suggest that the C-terminal subdomain might interact with a sub-terminal region of the viral DNA ([[literature:34709|Jenkins ''et al''. 1997]]; [[literature:30766|Heuer and Brown 1997]]; [[literature:20815|Esposito and Craigie 1998]]; [[literature:30765|Heuer and Brown 1998]]).

The functional structure of LTR retroelement-like INTs is already under study although it seems to be, together with a proviral DNA molecule and other viral and host proteins, part of a pre-integration complex of which little is known. Several studies suggest that this enzyme could act as a multimer or at least as a dimer (for a review in this topic see [[literature:15315|Craigie 2001]]).

<center>[[File:integrase1.jpg]]</center>
<center>HIV 1 INT 3D structure adapted from the PDB-file 1bis</center>

There are four known families of eukaryotic LTR retroelements – the ''Ty3/Gypsy'', the ''Ty1/Copia'', the ''Bel/Pao'', and the Retroviridae. The INT domain usually constitutes the C-terminal region of the pol polyprotein encoded by most but not all the elements belonging to the aforesaid pools. The exceptions are all the elements belonging to the ''Ty1/Copia'' group and several ''Ty3/Gypsy'' elements called ''Gmr1'' clade (for more details, see ([[literature:10126|Butler ''et al''. 2001]]; [[literature:26669|Goodwin & Poulter 2002]])), which display the INT domain, N-terminal to the RT, and also, other retroelement lineages, which do not encode for any type of known INT).

''Ty3/Gypsy'', ''Retroviridae'' and ''Bel/Pao'' INTs usually present the typical INT core followed by an additional module termed GPY/F that is firstly recognized by a preserved GPY/F motif that gives the name to this module ([[literature:46552|Malik and Eickbush 1999]]). The GPY/F module is thought to mediate multimerization ([[literature:88856|Ebina ''et al''. 2008]]).

<center>[[File:integrase2.jpg]]</center>

Adjacent to this module, some ''Ty3/Gypsy'' elements described in genomes of plants, fungi, and vertebrates incorporate an additional chromodomain similar to certain nuclear and chromatin-interacting proteins ([[literature:46552|Malik and Eickbush 1999]]). This finding inspired the term [[ty3gypsy_chromo|"Chromovirus"]] to describe chromodomain-containing integrase elements as a genus ([[literature:47259|Marin and Llorens 2000]]). The chromodomain (the chromatin organization modifier) is a small protein module involved in chromatin re-modeling, regulation of gene expression ([[literature:39429|Koonin ''et al''. 1995]]) and differential host genome integration of LTR retroelements ([[literature:85461|Wright ''et al''. 2005]]; [[literature: 70197|Singleton & Levin 2002]]).

<center>[[File:integrase3.jpg]]</center>

''Ty1/Copia'' INTs have not GPY/F module at their C-terminus but they usually present an additional module called GKGY ([[literature:46552|Malik & Eickbush 1999]]; [[literature:59075|Peterson-Burch & Voytas 2002]]; [[literature:24379|Gao & Voytas 2005]]).

<center>[[File:integrase4.jpg]]</center>

Although ''Ty1/Copia'' INT usually lack chromodomain features, recent research has revealed a particular clade of protist ''Ty1/Copia'' elements called ''CoDi-I'' (also called ''CoDi-A''), which also shows the occurrence of a chromodomain at their C-terminus (see [[literature:100685|Maumus ''et al''. 2009]]; [[literature:100596|Llorens ''et al''. 2009]]). Click [[Ty1/Copia| here]] for more information about the ''Ty1/Copia'' family.

There are two complementary classifications for the LTR retroelement INTs. Based on sequence these enzymes can be classified as DDE TRs and INTs. Based on INT-like structural potential similarities, the LTR retroelement INTs are members of the Retroviral Integrase Superfamily ([[literature:100803|Nowotny 2009]]) of nucleic acid-processing enzymes involved in; a) selfish evolution; b) replication and repair of DNA; c) recombination and gene fusion; d) RNA-mediated gene silencing; and e) oncogenesis.

Integrase - Revision history

imported>Gydbwiki at 15:13, 11 May 2011