2K6T

Solution structure of the relaxin-like factor

Summary for 2K6T

• Entry DOI: 10.2210/pdb2k6t/pdb
• Related: 2h8b 2K6U
• NMR Information: BMRB: 16901
• Descriptor: Insulin-like 3 A chain, Insulin-like 3 B chain (2 entities in total)
• Functional Keywords: protein, cleavage on pair of basic residues, disease mutation, hormone, polymorphism, secreted
• Cellular location: Secreted: P51460 P51460
• Total number of polymer chains: 2
• Total formula weight: 6306.31

Authors

Bullesbach, E.E.,Hass, M.A.S.,Jensen, M.R.,Hansen, D.F.,Kristensen, S.M.,Schwabe, C.,Led, J.J. (deposition date: 2008-07-23, release date: 2008-12-16, Last modification date: 2024-11-13)

Primary citation

Bullesbach, E.E.,Hass, M.A.S.,Jensen, M.R.,Hansen, D.F.,Kristensen, S.M.,Schwabe, C.,Led, J.J.
Solution structure of a conformationally restricted fully active derivative of the human relaxin-like factor
Biochemistry, 47:13308-13317, 2008

PubMed Abstract: Analogous to insulin, the relaxin-like factor (RLF) must undergo a structural transition to the active form prior to receptor binding. Thus, the C-terminus of the B chain of RLF folds toward the surface of the central B chain helix, causing partial obliteration of the two essential RLF receptor-binding site residues, valine B19 and tryptophan B27. Via comparison of the solution structure of a fully active C-terminally cross-linked RLF analogue with the native synthetic human RLF (hRLF), it became clear that the cross-linked analogue largely retains the essential folding of the native protein. Both proteins exist in a major and minor conformation, as revealed by multiple resonances from tryptophan B27 and adjacent residues on the B chain helix. Notably, the minor conformation is significantly more highly populated in the chemically cross-linked RLF than it is in the hRLF. In addition, compared to the unmodified molecule, subtle differences are observed within the B chain helix whereby the cross-linked derivative shows a reduced level of hydrogen bonding and significant peak broadening at the binding site residue ValB19. On the basis of these observations, we suggest that the solution structure of the native hormone represents an inactive conformer and that a dynamic equilibrium exists between the C-terminally unfolded binding conformation and the inactive conformation of the RLF.

PubMed: 19086273
DOI: 10.1021/bi801412w

Experimental method

SOLUTION NMR