4ZBN

Non-helical DNA Triplex Forms a Unique Aptamer Scaffold for High Affinity Recognition of Nerve Growth Factor

Summary for 4ZBN

• Entry DOI: 10.2210/pdb4zbn/pdb
• Descriptor: DNA (28-MER), Beta-nerve growth factor, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: complex, aptamer, immune system-dna complex, immune system/dna
• Biological source: Homo sapiens (Human); More
• Cellular location: Secreted: P01138
• Total number of polymer chains: 4
• Total formula weight: 46860.50

Authors

Davies, D.R.,Edwards, T.E. (deposition date: 2015-04-15, release date: 2015-06-10, Last modification date: 2024-10-23)

Primary citation

Jarvis, T.C.,Davies, D.R.,Hisaminato, A.,Resnicow, D.I.,Gupta, S.,Waugh, S.M.,Nagabukuro, A.,Wadatsu, T.,Hishigaki, H.,Gawande, B.,Zhang, C.,Wolk, S.K.,Mayfield, W.S.,Nakaishi, Y.,Burgin, A.B.,Stewart, L.J.,Edwards, T.E.,Gelinas, A.D.,Schneider, D.J.,Janjic, N.
Non-helical DNA Triplex Forms a Unique Aptamer Scaffold for High Affinity Recognition of Nerve Growth Factor.
Structure, 23:1293-1304, 2015

PubMed Abstract: Discerning the structural building blocks of macromolecules is essential for understanding their folding and function. For a new generation of modified nucleic acid ligands (called slow off-rate modified aptamers or SOMAmers), we previously observed essential functions of hydrophobic aromatic side chains in the context of well-known nucleic acid motifs. Here we report a 2.45-Å resolution crystal structure of a SOMAmer complexed with nerve growth factor that lacks any known nucleic acid motifs, instead adopting a configuration akin to a triangular prism. The SOMAmer utilizes extensive hydrophobic stacking interactions, non-canonical base pairing and irregular purine glycosidic bond angles to adopt a completely non-helical, compact S-shaped structure. Aromatic side chains contribute to folding by creating an unprecedented intercalating zipper-like motif and a prominent hydrophobic core. The structure provides compelling rationale for potent inhibitory activity of the SOMAmer and adds entirely novel motifs to the repertoire of structural elements uniquely available to SOMAmers.

PubMed: 26027732
DOI: 10.1016/j.str.2015.03.027

Experimental method

X-RAY DIFFRACTION (2.447 Å)