2KX8

NMR structure of stem-loop 4 from the human 7SK snRNA in complex with arginine

Summary for 2KX8

• Entry DOI: 10.2210/pdb2kx8/pdb
• Descriptor: 7SK, ARGININE (2 entities in total)
• Functional Keywords: snrna, rna
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 13624.15

Authors

Durney, M.A.,D'Souza, V.M. (deposition date: 2010-04-27, release date: 2010-09-08, Last modification date: 2024-05-01)

Primary citation

Durney, M.A.,D'Souza, V.M.
Preformed protein-binding motifs in 7SK snRNA: structural and thermodynamic comparisons with retroviral TAR.
J.Mol.Biol., 404:555-567, 2010

PubMed Abstract: The 7SK small nuclear RNA is a highly conserved non-coding RNA that regulates transcriptional elongation. 7SK utilizes the HEXIM proteins to sequester the transcription factor P-TEFb by a mechanism similar to that used by retroviral TAR RNA to engage Tat and P-TEFb. Tat has also recently been shown to bind 7SK directly and recruit P-TEFb to TAR. We report here the solution structures of the free and arginine-bound forms of stem loop 4 of 7SK (7SK-SL4). Comparison of the 7SK-SL4 and TAR structures demonstrates the presence of a common arginine sandwich motif. However, arginine binding to 7SK-SL4 is mechanistically distinct and occurs via docking into a pre-organized pocket resulting in a 1000-fold increased affinity. Furthermore, whereas formation of the binding pocket in TAR requires a critical base-triple, hydrogen-bond formation between the equivalent bases in 7SK-SL4 is not essential and the pocket is stabilized solely by a pseudo base-triple platform. In addition, this theme of preformed protein binding motifs also extends into the pentaloop. The configuration of the loop suggests that 7SK-SL4 is poised to make ternary contacts with P-TEFb and HEXIM or Tat. These key differences between 7SK-SL4 and TAR present an opportunity to understand RNA structural adaptation and have implications for understanding differential interactions with Tat.

PubMed: 20816986
DOI: 10.1016/j.jmb.2010.08.042

Experimental method

SOLUTION NMR