6k25

From Proteopedia

Crystal structure of Ca-unbound human Annexin A5 in low salt condition

Structural highlights

6k25 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.401Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ANXA5_HUMAN Defects in ANXA5 are associated with susceptibility to pregnancy loss, recurrent, type 3 (RPRGL3) [MIM:614391. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.^[1]

Function

ANXA5_HUMAN This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade.

Publication Abstract from PubMed

Annexins are soluble cytosolic proteins that bind to cell membranes. Annexin A5 self-assembles into a two-dimensional (2D) array and prevents cell rupture by attaching to damaged membranes. However, this process is not fully understood at the molecular level. In this study, we determined the crystal structures of annexin A5 with and without calcium (Ca(2+)) and confirmed the Ca(2+)-dependent outward motion of a tryptophan residue. Strikingly, the two structures exhibited the same crystal packing and 2D arrangement into a p3 lattice, which agrees well with the results of low-resolution structural imaging. High-resolution structures indicated that a three-fold interaction near the tryptophan residue is important for mediating the formation of the p3 lattice. A hypothesis on the promotion of p3 lattice formation by phosphatidyl serine (PS) is also suggested. This study provides molecular insight into how annexins modulate the physical properties of cell membranes as a function of Ca(2+) concentration and the phospholipid composition of the membrane.

High-resolution structures of annexin A5 in a two-dimensional array.,Hong S, Na S, Kim OH, Jeong S, Oh BC, Ha NC J Struct Biol. 2020 Jan 1;209(1):107401. doi: 10.1016/j.jsb.2019.10.003. Epub, 2019 Oct 9. PMID:31605770^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bogdanova N, Horst J, Chlystun M, Croucher PJ, Nebel A, Bohring A, Todorova A, Schreiber S, Gerke V, Krawczak M, Markoff A. A common haplotype of the annexin A5 (ANXA5) gene promoter is associated with recurrent pregnancy loss. Hum Mol Genet. 2007 Mar 1;16(5):573-8. Epub 2007 Mar 5. PMID:17339269 doi:10.1093/hmg/ddm017
↑ Hong S, Na S, Kim OH, Jeong S, Oh BC, Ha NC. High-resolution structures of annexin A5 in a two-dimensional array. J Struct Biol. 2020 Jan 1;209(1):107401. doi: 10.1016/j.jsb.2019.10.003. Epub, 2019 Oct 9. PMID:31605770 doi:http://dx.doi.org/10.1016/j.jsb.2019.10.003