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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7213
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pubmed:dateCreated |
2008-10-3
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pubmed:abstractText |
HIV-1 protease processes the Gag and Gag-Pol polyproteins into mature structural and functional proteins, including itself, and is therefore indispensable for viral maturation. The mature protease is active only as a dimer with each subunit contributing catalytic residues. The full-length transframe region protease precursor appears to be monomeric yet undergoes maturation via intramolecular cleavage of a putative precursor dimer, concomitant with the appearance of mature-like catalytic activity. How such intramolecular cleavage can occur when the amino and carboxy termini of the mature protease are part of an intersubunit beta-sheet located distal from the active site is unclear. Here we visualize the early events in N-terminal autoprocessing using an inactive mini-precursor with a four-residue N-terminal extension that mimics the transframe region protease precursor. Using paramagnetic relaxation enhancement, a technique that is exquisitely sensitive to the presence of minor species, we show that the mini-precursor forms highly transient, lowly populated (3-5%) dimeric encounter complexes that involve the mature dimer interface but occupy a wide range of subunit orientations relative to the mature dimer. Furthermore, the occupancy of the mature dimer configuration constitutes a very small fraction of the self-associated species (accounting for the very low enzymatic activity of the protease precursor), and the N-terminal extension makes transient intra- and intersubunit contacts with the substrate binding site and is therefore available for autocleavage when the correct dimer orientation is sampled within the encounter complex ensemble.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-10438521,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-10467100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-11013762,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-12238594,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-12933791,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-15125681,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-15280456,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-16642002,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-17051159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-17084097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-17146057,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-17412697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-17586318,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-17960247,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-1799632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-18321978,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-2686029,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-8058744,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-8110758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-8352596,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-8626801,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-9525682,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-9646869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18833280-9811541
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1476-4687
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
2
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pubmed:volume |
455
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
693-6
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pubmed:dateRevised |
2010-9-21
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pubmed:meshHeading |
pubmed-meshheading:18833280-Dimerization,
pubmed-meshheading:18833280-HIV Protease,
pubmed-meshheading:18833280-HIV-1,
pubmed-meshheading:18833280-Models, Molecular,
pubmed-meshheading:18833280-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:18833280-Protein Precursors,
pubmed-meshheading:18833280-Protein Processing, Post-Translational,
pubmed-meshheading:18833280-Protein Structure, Tertiary,
pubmed-meshheading:18833280-Spin Labels,
pubmed-meshheading:18833280-gag Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2008
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pubmed:articleTitle |
Visualizing transient events in amino-terminal autoprocessing of HIV-1 protease.
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pubmed:affiliation |
Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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