Effect of G40R mutation on the binding of human SRY protein to DNA: A molecular dynamics view

✍ Scribed by Yun Tang; Lennart Nilsson

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 814 KB
• Volume: 35
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/(sici)1097-0134(19990401)35:1<101::aid-prot10>3.0.co;2-5

✦ Synopsis

Molecular dynamics simulation was conducted to investigate the reason why the mutant G40R of hSRY protein has a low affinity for DNA. Compared with the previous dynamics results of the wild-type hSRY-HMG-DNA complex, the results of molecular dynamics simulation on the mutant G40R hSRY-HMG-DNA system demonstrated that the whole structure of DNA (especially the second strand) had a major deviation away from the short arm of the HMG box. Consequently, the DNA and the mutant protein could not specifically recognize each other, that is, very different, and low-occupancy, direct, and water-mediated hydrogen bonds were detected at the protein-DNA interface, no conformational changes occurred at the loop region around Met9 during the simulation, and residue IIe13 did not intercalate between the bases of A5 and A6. These results indicated that the mutant G40R did not form a specific complex with the DNA target, hence led to complete gonadal dysgenesis. From the simulation, we realized that the residue Gly40 played a critical structural role in the hSRY-DNA recognition. It might be a structural supporting point of DNA binding because of the absence of a side chain. The reason for the difficulty of the mutant G40R to form a complex with DNA might be that the long and positively charged side chain of Arg40 by its bulk and positive charge hindered the DNA's access to the active sites of the protein.