Limits...
Imperfect DNA mirror repeats in the gag gene of HIV-1 (HXB2) identify key functional domains and coincide with protein structural elements in each of the mature proteins.

Lang DM - Virol. J. (2007)

Bottom Line: However, imperfect mirror repeats (IMRs) having > or = 50% symmetry are common in the protein coding DNA of monomeric proteins and their distribution has been found to coincide with protein structural elements - helices, beta sheets and turns.Throughout the protein, IMRs coincide with functionally significant segments of the protein.The frequency and distribution of IMRs in HIV-1 Gag indicates that DNA symmetry is a fundamental property of protein coding DNA and that different levels of symmetry are associated with different functional aspects of the gene and its protein.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Contemporary Sciences, University of Abertay-Dundee, Bell Street, Dundee DD1 1HG, Scotland, UK. dml_mail@yahoo.com

ABSTRACT

Background: A DNA mirror repeat is a sequence segment delimited on the basis of its containing a center of symmetry on a single strand, e.g. 5'-GCATGGTACG-3'. It is most frequently described in association with a functionally significant site in a genomic sequence, and its occurrence is regarded as noteworthy, if not unusual. However, imperfect mirror repeats (IMRs) having > or = 50% symmetry are common in the protein coding DNA of monomeric proteins and their distribution has been found to coincide with protein structural elements - helices, beta sheets and turns. In this study, the distribution of IMRs is evaluated in a polyprotein - to determine whether IMRs may be related to the position or order of protein cleavage or other hierarchal aspects of protein function. The gag gene of HIV-1 [GenBank:K03455] was selected for the study because its protein motifs and structural components are well documented.

Results: There is a highly specific relationship between IMRs and structural and functional aspects of the Gag polyprotein. The five longest IMRs in the polyprotein translate a key functional segment in each of the five cleavage products. Throughout the protein, IMRs coincide with functionally significant segments of the protein. A detailed annotation of the protein, which combines structural, functional and IMR data illustrates these associations. There is a significant statistical correlation between the ends of IMRs and the ends of PSEs in each of the mature proteins. Weakly symmetric IMRs (> or 33%) are related to cleavage positions and processes.

Conclusion: The frequency and distribution of IMRs in HIV-1 Gag indicates that DNA symmetry is a fundamental property of protein coding DNA and that different levels of symmetry are associated with different functional aspects of the gene and its protein. The interaction between IMRs and protein structure and function is precise and interwoven over the entire length of the polyprotein. The distribution of IMRs and their relationship to structural and functional motifs in the protein that they translate, suggest that DNA-driven processes, including the selection of mirror repeats, may be a constraining factor in molecular evolution.

Show MeSH

Related in: MedlinePlus

The distribution of mIMRs in the immature Gag protein [NCBI:1L6N, [8]]. MIMRs that are ≥ 50% symmetric are noticeably absent from some segments of the protein. These regions are characterized by a series of rdIMRs, arranged end-to-end (illustrated in black). The spans lacking mIMRs are highly reactive and mobile. The A3..C87 region of matrix undergoes structural transformation at several stages of the virion life cycle, and contains basic residues that target Gag to the plasma membrane [9], a calmodulin-binding motif [10] and a nuclear localization signal [11]. The T204..E245 region of capsid includes the exposed loop on the virion core [8, 12], and the CypA binding site [12].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2211468&req=5

Figure 1: The distribution of mIMRs in the immature Gag protein [NCBI:1L6N, [8]]. MIMRs that are ≥ 50% symmetric are noticeably absent from some segments of the protein. These regions are characterized by a series of rdIMRs, arranged end-to-end (illustrated in black). The spans lacking mIMRs are highly reactive and mobile. The A3..C87 region of matrix undergoes structural transformation at several stages of the virion life cycle, and contains basic residues that target Gag to the plasma membrane [9], a calmodulin-binding motif [10] and a nuclear localization signal [11]. The T204..E245 region of capsid includes the exposed loop on the virion core [8, 12], and the CypA binding site [12].

Mentions: MIMRs and rdIMRs vary in distribution, beyond that which would occur due to the differences in their lengths. MIMRs occur throughout most of gag, as a series of overlapping, or nearly overlapping spans; within many mIMRs, there are one or two spatially separated rdIMRs. MIMRs are, however, noticeably absent in some segments of gag; in these segments, e.g. M1..R91 (MA) and P133..G248 (CA), rdIMRs form a nearly continuous series, end-to-end. The sequence spans in MA and CA that do not contain mIMRs are illustrated in Figure 1. These regions are both highly reactive and mobile (detailed in the legend).


Imperfect DNA mirror repeats in the gag gene of HIV-1 (HXB2) identify key functional domains and coincide with protein structural elements in each of the mature proteins.

Lang DM - Virol. J. (2007)

The distribution of mIMRs in the immature Gag protein [NCBI:1L6N, [8]]. MIMRs that are ≥ 50% symmetric are noticeably absent from some segments of the protein. These regions are characterized by a series of rdIMRs, arranged end-to-end (illustrated in black). The spans lacking mIMRs are highly reactive and mobile. The A3..C87 region of matrix undergoes structural transformation at several stages of the virion life cycle, and contains basic residues that target Gag to the plasma membrane [9], a calmodulin-binding motif [10] and a nuclear localization signal [11]. The T204..E245 region of capsid includes the exposed loop on the virion core [8, 12], and the CypA binding site [12].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2211468&req=5

Figure 1: The distribution of mIMRs in the immature Gag protein [NCBI:1L6N, [8]]. MIMRs that are ≥ 50% symmetric are noticeably absent from some segments of the protein. These regions are characterized by a series of rdIMRs, arranged end-to-end (illustrated in black). The spans lacking mIMRs are highly reactive and mobile. The A3..C87 region of matrix undergoes structural transformation at several stages of the virion life cycle, and contains basic residues that target Gag to the plasma membrane [9], a calmodulin-binding motif [10] and a nuclear localization signal [11]. The T204..E245 region of capsid includes the exposed loop on the virion core [8, 12], and the CypA binding site [12].
Mentions: MIMRs and rdIMRs vary in distribution, beyond that which would occur due to the differences in their lengths. MIMRs occur throughout most of gag, as a series of overlapping, or nearly overlapping spans; within many mIMRs, there are one or two spatially separated rdIMRs. MIMRs are, however, noticeably absent in some segments of gag; in these segments, e.g. M1..R91 (MA) and P133..G248 (CA), rdIMRs form a nearly continuous series, end-to-end. The sequence spans in MA and CA that do not contain mIMRs are illustrated in Figure 1. These regions are both highly reactive and mobile (detailed in the legend).

Bottom Line: However, imperfect mirror repeats (IMRs) having > or = 50% symmetry are common in the protein coding DNA of monomeric proteins and their distribution has been found to coincide with protein structural elements - helices, beta sheets and turns.Throughout the protein, IMRs coincide with functionally significant segments of the protein.The frequency and distribution of IMRs in HIV-1 Gag indicates that DNA symmetry is a fundamental property of protein coding DNA and that different levels of symmetry are associated with different functional aspects of the gene and its protein.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Contemporary Sciences, University of Abertay-Dundee, Bell Street, Dundee DD1 1HG, Scotland, UK. dml_mail@yahoo.com

ABSTRACT

Background: A DNA mirror repeat is a sequence segment delimited on the basis of its containing a center of symmetry on a single strand, e.g. 5'-GCATGGTACG-3'. It is most frequently described in association with a functionally significant site in a genomic sequence, and its occurrence is regarded as noteworthy, if not unusual. However, imperfect mirror repeats (IMRs) having > or = 50% symmetry are common in the protein coding DNA of monomeric proteins and their distribution has been found to coincide with protein structural elements - helices, beta sheets and turns. In this study, the distribution of IMRs is evaluated in a polyprotein - to determine whether IMRs may be related to the position or order of protein cleavage or other hierarchal aspects of protein function. The gag gene of HIV-1 [GenBank:K03455] was selected for the study because its protein motifs and structural components are well documented.

Results: There is a highly specific relationship between IMRs and structural and functional aspects of the Gag polyprotein. The five longest IMRs in the polyprotein translate a key functional segment in each of the five cleavage products. Throughout the protein, IMRs coincide with functionally significant segments of the protein. A detailed annotation of the protein, which combines structural, functional and IMR data illustrates these associations. There is a significant statistical correlation between the ends of IMRs and the ends of PSEs in each of the mature proteins. Weakly symmetric IMRs (> or 33%) are related to cleavage positions and processes.

Conclusion: The frequency and distribution of IMRs in HIV-1 Gag indicates that DNA symmetry is a fundamental property of protein coding DNA and that different levels of symmetry are associated with different functional aspects of the gene and its protein. The interaction between IMRs and protein structure and function is precise and interwoven over the entire length of the polyprotein. The distribution of IMRs and their relationship to structural and functional motifs in the protein that they translate, suggest that DNA-driven processes, including the selection of mirror repeats, may be a constraining factor in molecular evolution.

Show MeSH
Related in: MedlinePlus