Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.56 (
insulin-degrading enzyme
)
737
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
As part of the Pr55
Gag
polyprotein, p6 fulfills an essential role in the late steps of the replication cycle. However, almost nothing is known about the functions of the mature HIV-1 p6 protein. Recently, we showed that p6 is a bona fide substrate of the
insulin-degrading enzyme
(
IDE
), a ubiquitously expressed zinc metalloprotease. This phenomenon appears to be specific for HIV-1, since p6 homologs of HIV-2, SIV and EIAV were
IDE
-insensitive. Furthermore, abrogation of the
IDE
-mediated degradation of p6 reduces the replication capacity of HIV-1 in an Env-dependent manner. However, it remained unclear to which extent the
IDE
mediated degradation is phylogenetically conserved among HIV-1. Here, we describe two HIV-1 isolates with
IDE
resistant p6 proteins. Sequence comparison allowed deducing one single amino acid regulating
IDE
sensitivity of p6. Exchanging the N-terminal leucine residue of p6 derived from the
IDE
sensitive isolate HIV-1
NL4
-3
with proline enhances its stability, while replacing Pro-1 of p6 from the
IDE
insensitive isolate SG3 with leucine restores susceptibility towards
IDE
. Phylogenetic analyses of this natural polymorphism revealed that the N-terminal leucine is characteristic for p6 derived from HIV-1 group M except for subtype A, which predominantly expresses p6 with an N-terminal proline. Consequently, p6 peptides derived from subtype A are not degraded by
IDE
. Thus,
IDE
mediated degradation of p6 is specific for HIV-1 group M isolates and not occasionally distributed among HIV-1.
...
PMID:The N-Terminus of the HIV-1 p6 Gag Protein Regulates Susceptibility to Degradation by IDE. 3054 91
