Crystal Structure of Okadaic Acid Binding Protein 2.1: A Sponge Protein Implicated in Cytotoxin Accumulation

• Published in: Chembiochem : a European journal of chemical biology Vol. 16; no. 10; pp. 1435 - 1439
• Main Authors: Ehara, Haruhiko, Makino, Marie, Kodama, Koichiro, Konoki, Keiichi, Ito, Takuhiro, Sekine, Shun-ichi, Fukuzawa, Seketsu, Yokoyama, Shigeyuki, Tachibana, Kazuo
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 06-07-2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Aequorin - chemistry; Amino Acid Sequence; Animals; Crystal structure; Crystallography, X-Ray; Cytotoxins - metabolism; Enzyme Inhibitors - metabolism; marine cytotoxins; Models, Molecular; Molecular Docking Simulation; Molecular Sequence Data; okadaic acid; Okadaic Acid - metabolism; Porifera - chemistry; Porifera - metabolism; Protein Binding; Protein Conformation; protein structure; Proteins; Proteins - chemistry; Proteins - metabolism; Rodents; Sequence Alignment; sponges; marine cytotoxins; protein structure; sponges; okadaic acid
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.201500141

Okadaic acid (OA) is a marine polyether cytotoxin that was first isolated from the marine sponge Halichondria okadai. OA is a potent inhibitor of protein serine/threonine phosphatases (PP) 1 and 2A, and the structural basis of phosphatase inhibition has been well investigated. However, the role and mechanism of OA retention in the marine sponge have remained elusive. We have solved the crystal structure of okadaic acid binding protein 2.1 (OABP2.1) isolated from H. okadai; it has strong affinity for OA and limited sequence homology to other proteins. The structure revealed that OABP2.1 consists of two α‐helical domains, with the OA molecule deeply buried inside the protein. In addition, the global fold of OABP2.1 was unexpectedly similar to that of aequorin, a jellyfish photoprotein. The presence of structural homologues suggested that, by using similar protein scaffolds, marine invertebrates have developed diverse survival systems adapted to their living environments.
Toxin encapsulation: The structure of a toxin binding protein from a marine sponge reveals a molecular mechanism for toxin entrapment and delivery to predators. The unexpected structural similarity with aequorin also highlights the diverse survival systems of marine invertebrates.