View source for 2vaf

[[Image:2vaf.jpg|left|200px]]<br /><applet load="2vaf" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="2vaf, resolution 3.8&Aring;" />
'''CRYSTAL STRUCTURE OF HUMAN CARDIAC CALSEQUESTRIN'''<br />

==Overview==
Mutations of conserved residues of human cardiac calsequestrin (hCSQ2), a, high-capacity, low-affinity Ca(2+)-binding protein in the sarcoplasmic, reticulum, have been associated with catecholamine-induced polymorphic, ventricular tachycardia (CPVT). In order to understand the molecular, mechanism and pathophysiological link between these CPVT-related missense, mutations of hCSQ2 and the resulting arrhythmias, we generated three, CPVT-causing mutants of hCSQ2 (R33Q, L167H, and D307H) and two, non-pathological mutants (T66A and V76M) and investigated the effect of, these mutations. In addition, we determined the crystal structure of the, corresponding wild-type hCSQ2 to gain insight into the structural effects, of those mutations. Our data show clearly that all three CPVT-related, mutations lead to significant reduction in Ca(2+)-binding capacity in, spite of the similarity of their secondary structures to that of the, wild-type hCSQ2. Light-scattering experiments indicate that the, Ca(2+)-dependent monomer-polymer transitions of the mutants are quite, different, confirming that the linear polymerization behavior of CSQ is, linked directly to its high-capacity Ca(2+) binding. R33Q and D307H, mutations result in a monomer that appears to be unable to form a properly, oriented dimer. On the other hand, the L167H mutant has a disrupted, hydrophobic core in domain II, resulting in high molecular aggregates, which cannot respond to Ca(2+). Although one of the non-pathological, mutants, T66A, shares characteristics with the wild-type, the other null, mutant, V76M, shows significantly altered Ca(2+)-binding and, polymerization behaviors, calling for careful reconsideration of its, status.

==About this Structure==
2VAF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure superseeds the now removed PDB entry 2V0Q. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VAF OCA]. 

==Reference==
Characterization of Human Cardiac Calsequestrin and its Deleterious Mutants., Kim E, Youn B, Kemper L, Campbell C, Milting H, Varsanyi M, Kang C, J Mol Biol. 2007 Aug 29;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17881003 17881003]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Campbell, C.]]
[[Category: Kang, C.]]
[[Category: Kemper, L.]]
[[Category: Kim, E.]]
[[Category: Milting, H.]]
[[Category: Varsanyi, M.]]
[[Category: Youn, B.]]
[[Category: calcium]]
[[Category: crystal structure human cardiac calsequestrin]]
[[Category: disease mutation]]
[[Category: glycoprotein]]
[[Category: metal-binding protein]]
[[Category: muscle protein]]
[[Category: polymorphism]]
[[Category: sarcoplasmic reticulum]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:51:37 2008''