View source for 4om5


==Crystal structure of CTX A4 from Taiwan Cobra (Naja naja atra)==
<StructureSection load='4om5' size='340' side='right'caption='[[4om5]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4om5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Naja_atra Naja atra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OM5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OM5 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4om4|4om4]]</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=4om5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4om5 OCA], [http://pdbe.org/4om5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4om5 RCSB], [http://www.ebi.ac.uk/pdbsum/4om5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4om5 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/CTXA4_NAJAT CTXA4_NAJAT]] Basic protein that bind to cell membrane and depolarizes cardiomyocytes. This cytotoxin also shows lytic activities, but 2-fold more important than that of CTX-A2. It binds to the integrin alpha-V/beta-3 with a moderate affinity. Inhibits protein kinase C. It may interact with sulfatides in the cell membrane, which induces pore formation and cell internalization and is responsible for cytotoxicity in cardiomyocytes. It also may target the mitochondrial membrane and induces mitochondrial swelling and fragmentation.<ref>PMID:8448165</ref> <ref>PMID:16407244</ref> <ref>PMID:9398182</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cobra cardiotoxins (CTXs) are a family of three-fingered basic polypeptides known to interact with diverse targets such as heparan sulfates, sulfatides and integrins on cell surfaces. After CTXs bind to the membrane surface, they are internalized to intracellular space and exert their cytotoxicity with an unknown mechanism. By the combined in vitro kinetic binding, 3D X-ray structure determination, and cell biology studies on the naturally abundant CTX homologues from the Taiwanese cobra, we showed that slight variations on the spatial distribution of positively charged or hydrophobic domains among CTX A2, A3 and A4 could lead to significant changes in their endocytotic pathways and action mechanisms via distinct sulfated glycoconjugates mediated processes. The intracellular locations of these structurally similar CTXs after internalization are shown to vary between the mitochondria and lysosomes via either dynamin2-dependent or -independent processes with distinct membrane cholesterol sensitivity. Evidence is presented to suggest that the shifting between the sulfated glycoconjugates as distinct targets of CTX A2, A3 and A4 might play roles in the co-evolutionary arms race between venomous snake toxins to cope with different membrane repair mechanisms at the cellular levels. The sensitivity of endocytotic routes to the spatial distribution of positively charged or hydrophobic domains may provide an explanation for the diverse endocytosis pathways of other cell-penetrating basic polypeptides.

Endocytotic Routes of Cobra Cardiotoxins Depend on the Spatial Distribution of Positively Charged and Hydrophobic Domains to Target Distinct Types of Sulfated Glycoconjugates on Cell Surface.,Lee SC, Lin CC, Wang CH, Wu PL, Huang HW, Chang CI, Wu WG J Biol Chem. 2014 Jun 4. pii: jbc.M114.557157. PMID:24898246<ref>PMID:24898246</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4om5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cardiotoxin 3D structures|Cardiotoxin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Naja atra]]
[[Category: Chang, C I]]
[[Category: Lin, C C]]
[[Category: Wu, W G]]
[[Category: Endocytosis]]
[[Category: Five beta sheet]]
[[Category: Heparan sulfate]]
[[Category: Heparin]]
[[Category: Three functional loop]]
[[Category: Toxin]]