Pre-structured motifs in the natively unstructured preS1 surface antigen of hepatitis B virus.
The preS1 surface antigen of hepatitis B virus (HBV) is known to play an important role in the initial attachment of HBV to hepatocytes. We have characterized structural features of the full-length preS1 using heteronuclear NMR methods and discovered that this 119-residue protein is inherently unstructured without a unique tertiary structure under a nondenaturing condition. Yet, combination of various NMR parameters shows that the preS1 contains "pre-structured" domains broadly covering its functional domains. The most prominent domain is formed by residues 27-45 and overlaps with the putative hepatocyte-binding domain (HBD) encompassing residues 21-47, within which two well-defined pre-structured motifs, formed by Pro(32)-Ala(36) and Pro(41)-Phe(45) are found. Additional, somewhat less prominent, pre-structured motifs are also formed by residues 11-18, 22-25, 37-40, and 46-50. Overall results suggest that the preS1 is a natively unstructured protein (NUP) whose N-terminal 50 residues, populated with multiple pre-structured motifs, contribute critically to hepatocyte binding.
Chi
Seung-Wook
SW
Molecular Cancer Research Center, Division of Molecular Therapeutics, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Kim
Do-Hyoung
DH
Lee
Si-Hyung
SH
Chang
Iksoo
I
Han
Kyou-Hoon
KH
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D006514:Hepatitis B Surface Antigens / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011498:Protein Precursors / Q000737:chemistry*
D006514:Hepatitis B Surface Antigens; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen