title: Structural insight into the interaction between the Hox and HMGB1 and understanding of the HMGB1-enhancing effect of Hox-DNA binding.
abstract: The Hox DNA binding domain, the homeodomain, plays critical roles in genetic control of development and cell fate determination. The variable regulatory functions of Hox proteins are accomplished by binding to target DNA sequences and collaborating protein partners that includes human high mobility group B1 (HMGB1). To better understand the interaction between Hox and HMGB1 and the facilitation of Hox-DNA binding by HMGB1, we solved the solution structure of the homeodomain of Hox including the N-terminal arm region (Hoxc9DBD hereafter). In addition, the details of the interaction between these two proteins, as well as DNA binding of the Hox-HMGB1 complex, were investigated by NMR, ITC, and EMSA. The results suggest that binding of the HMGB1 A-box to Hoxc9DBD makes the loop-1 (loop preceding helix-2 of Hoxc9DBD) more access to DNA backbone, which facilitate Hox-DNA binding with enhanced affinity.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Hyun-Hwi
authors.initials: HH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Gachon University, 534-2 Yeonsu-dong, Yeonsu-gu, Incheon, Republic of Korea.
authors.forename: Sung Jean
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Han
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Chinar
authors.initials: C
authors.lastname: Pathak
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute, 804-1 Yangcheong-Ri, Ochang, Chungbuk 306-883, Republic of Korea.
authors.forename: Hae-Kap
authors.initials: HK
authors.lastname: Cheong
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea. Electronic address: lbj@nmr.snu.ac.kr.
authors.forename: Bong-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D024243:HMGB1 Protein / Q000737:chemistry* / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary
chemical_list: D024243:HMGB1 Protein; D018398:Homeodomain Proteins; C522807:Hoxc9 protein, human; D004247:DNA
keywords: HMGB1; Homeodomain; Hox; NMR; Transcription