6B3I

Annexin A13a

Summary for 6B3I

• Entry DOI: 10.2210/pdb6b3i/pdb
• Descriptor: Annexin, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: annexin, lipid binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 116846.34

Authors

McCulloch, K.M.,Iverson, T.M. (deposition date: 2017-09-21, release date: 2018-10-10, Last modification date: 2024-11-06)

Primary citation

McCulloch, K.M.,Yamakawa, I.,Shifrin Jr., D.A.,McConnell, R.E.,Foegeding, N.J.,Singh, P.K.,Mao, S.,Tyska, M.J.,Iverson, T.M.
An alternative N-terminal fold of the intestine-specific annexin A13a induces dimerization and regulates membrane-binding.
J. Biol. Chem., 294:3454-3463, 2019

PubMed Abstract: Annexin proteins function as Ca-dependent regulators of membrane trafficking and repair that may also modulate membrane curvature. Here, using high-resolution confocal imaging, we report that the intestine-specific annexin A13 (ANX A13) localizes to the tips of intestinal microvilli and determined the crystal structure of the ANX A13a isoform to 2.6 Å resolution. The structure revealed that the N terminus exhibits an alternative fold that converts the first two helices and the associated helix-loop-helix motif into a continuous α-helix, as stabilized by a domain-swapped dimer. We also found that the dimer is present in solution and partially occludes the membrane-binding surfaces of annexin, suggesting that dimerization may function as a means for regulating membrane binding. Accordingly, as revealed by binding and cellular localization assays, ANX A13a variants that favor a monomeric state exhibited increased membrane association relative to variants that favor the dimeric form. Together, our findings support a mechanism for how the association of the ANX A13a isoform with the membrane is regulated.

PubMed: 30610115
DOI: 10.1074/jbc.RA118.004571

Experimental method

X-RAY DIFFRACTION (2.6 Å)