We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

4bmg

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_4bmg| PDB=4bmg | SCENE= }}
+
==Crystal structure of hexameric HBc149 Y132A==
-
===Crystal structure of hexameric HBc149 Y132A===
+
<StructureSection load='4bmg' size='340' side='right' caption='[[4bmg]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
-
{{ABSTRACT_PUBMED_23824290}}
+
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4bmg]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_b_virus Hepatitis b virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BMG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BMG FirstGlance]. <br>
 +
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bmg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bmg RCSB], [http://www.ebi.ac.uk/pdbsum/4bmg PDBsum]</span></td></tr>
 +
</table>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
HBc, the capsid-forming "core protein" of human hepatitis B virus (HBV), is a multidomain, alpha-helical homodimer that aggressively forms human HBV capsids. Structural plasticity has been proposed to be important to the myriad functions HBc mediates during viral replication. Here, we report detailed thermodynamic analyses of the folding of the dimeric HBc protomer under conditions that prevented capsid formation. Central to our success was the use of ion mobility spectrometry-mass spectrometry and microscale thermophoresis, which allowed folding mechanisms to be characterized using just micrograms of protein. HBc folds in a three-state transition with a stable, dimeric, alpha-helical intermediate. Extensive protein engineering showed thermodynamic linkage between different structural domains. Unusual effects associated with mutating some residues suggest structural strain, arising from frustrated contacts, is present in the native dimer. We found evidence of structural gatekeepers that, when mutated, alleviated native strain and prevented (or significantly attenuated) capsid formation by tuning the population of alternative native conformations. This strain is likely an evolved feature that helps HBc access the different structures associated with its diverse essential functions. The subtle balance between native and strained contacts may provide the means to tune conformational properties of HBc by molecular interactions or mutations, thereby conferring allosteric regulation of structure and function. The ability to trap HBc conformers thermodynamically by mutation, and thereby ablate HBV capsid formation, provides proof of principle for designing antivirals that elicit similar effects.
-
==Function==
+
Thermodynamic origins of protein folding, allostery, and capsid formation in the human hepatitis B virus core protein.,Alexander CG, Jurgens MC, Shepherd DA, Freund SM, Ashcroft AE, Ferguson N Proc Natl Acad Sci U S A. 2013 Jul 3. PMID:23824290<ref>PMID:23824290</ref>
-
[[http://www.uniprot.org/uniprot/CAPSD_HBVD1 CAPSD_HBVD1]] Self assembles to form an icosahedral capsid. Most capsid appear to be large particles with a icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsid are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stucked in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genome for transcription, or bud through the endoplasmic reticulum to provide new virions (By similarity).<ref>PMID:7711014</ref> Encapsidates hepatitis delta genome (By similarity).<ref>PMID:7711014</ref>
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[4bmg]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Hepatitis_b_virus Hepatitis b virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BMG OCA].
+
</div>
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:023824290</ref><references group="xtra"/><references/>
+
__TOC__
 +
</StructureSection>
[[Category: Hepatitis b virus]]
[[Category: Hepatitis b virus]]
-
[[Category: Alexander, C G.]]
+
[[Category: Alexander, C G]]
-
[[Category: Ashcroft, A E.]]
+
[[Category: Ashcroft, A E]]
-
[[Category: Ferguson, N.]]
+
[[Category: Ferguson, N]]
-
[[Category: Juergens, M C.]]
+
[[Category: Juergens, M C]]
-
[[Category: Shepherd, D A.]]
+
[[Category: Shepherd, D A]]
[[Category: Allostery]]
[[Category: Allostery]]
[[Category: Protein folding]]
[[Category: Protein folding]]
[[Category: Viral protein]]
[[Category: Viral protein]]

Revision as of 10:07, 21 December 2014

Crystal structure of hexameric HBc149 Y132A

4bmg, resolution 3.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bmg"
Personal tools