| dc.creator |
Sáez-Cirión, Asier |
|
| dc.creator |
Arrondo, José Luis R. |
|
| dc.creator |
Gómara, María J. |
|
| dc.creator |
Lorizate, Maier |
|
| dc.creator |
Iloro, Ibon |
|
| dc.creator |
Melikyan, Grigory |
|
| dc.creator |
Nieva, José L. |
|
| dc.date |
2008-04-14T06:47:39Z |
|
| dc.date |
2008-04-14T06:47:39Z |
|
| dc.date |
2003-12 |
|
| dc.date.accessioned |
2017-01-31T01:02:10Z |
|
| dc.date.available |
2017-01-31T01:02:10Z |
|
| dc.identifier |
Biophys J. 2003 December; 85(6): 3769–3780 |
|
| dc.identifier |
1542-0086 |
|
| dc.identifier |
http://hdl.handle.net/10261/3555 |
|
| dc.identifier.uri |
http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3555 |
|
| dc.description |
Copyright © by Biophysical Society. Final full-text version of the paper available at: http://www.biophysj.org/cgi/content/abstract/85/6/3769 |
|
| dc.description |
The membrane-proximal segment connecting the helical core with the transmembrane anchor of human
immunodeficiency virus type 1 gp41 is accessible to broadly neutralizing antibodies and plays a crucial role in fusion activity.
New predictive approaches including computation of interfacial affinity and the corresponding hydrophobic moments suggest
that this region is functionally segmented into two consecutive subdomains: one amphipathic at the N-terminal side and one
fully interfacial at the C-terminus. The N-terminal subdomain would extend a-helices from the preceding carboxy-terminal
heptad repeat and provide, at the same time, a hydrophobic-at-interface surface. Experiments were performed to compare
a wild-type representing pretransmembrane peptide with a nonamphipathic defective sequence, which otherwise conserved
interfacial hydrophobicity at the carboxy-subdomain. Results confirmed that both penetrated equally well into lipid monolayers
and both were able to partition into membrane interfaces. However only the functional sequence: 1), adopted helical structures
in solution and in membranes; 2), formed homo-oligomers in solution and membranes; and 3), inhibited gp41-induced cell-cell
fusion. These data support two roles for gp41 aromatic-rich pretransmembrane sequence: 1), oligomerization of gp41; and 2),
immersion into the viral membrane interface. Accessibility to membrane interfaces and subsequent adoption of the low-energy
structure may augment helical bundle formation and perhaps be related to a concomitant loss of immunoreactivity. These
results may have implications in the development of HIV-1 fusion inhibitors and vaccines. |
|
| dc.description |
This work was supported by Spanish Ministerio de Ciencia y Tecnologı´a
(EET 2001-1954), the Basque Government (PI-1999-7), and the University
of the Basque Country (UPV 042.310-13552/2001). A.S.C. was recipient of
a predoctoral fellowship of the Basque Government. G. Melikyan was
supported by National Institutes of Health grant GM54787. |
|
| dc.description |
Peer reviewed |
|
| dc.format |
261531 bytes |
|
| dc.format |
application/pdf |
|
| dc.language |
eng |
|
| dc.publisher |
Biophysical Society |
|
| dc.rights |
openAccess |
|
| dc.title |
Structural and Functional Roles of HIV-1 gp41 Pretransmembrane Sequence Segmentation |
|
| dc.type |
Artículo |
|