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Response of SCP-2L domain of human MFE-2 to ligand removal: Binding site closure and burial of peroxisomal targeting signal

par Lensink, Marc ;Haapalainen, Antti A.M.;Hiltunen, Kalervo J.K.;Glumoff, Tuomo;Juffer, André A.H.
Référence Journal of Molecular Biology, 323, 1, page (99-113)
Publication Publié, 2002

Article révisé par les pairs

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Résumé :

In the study of the structure and function relationship of human MFE-2, we have investigated the dynamics of human MFE-2SCP-2L (hSCP-2L) and its response to ligand removal. A comparison was made with homologous rabbit SCP-2. Breathing and a closing motion are found, identifiable with an adjustment in size and a closing off of the binding pocket. Crucial residues for structural integrity have been identified. Particularly mobile areas of the protein are loop 1 that is connecting helices A and C in space, and helix D, next to the entrance of the pocket. In hSCP-2L, the binding pocket gets occupied by Phe93, which is making a tight hydrophobic contact with Trp36. In addition, it is found that the C-terminal peroxisomal targeting signal (PTS1) that is solvent exposed in the complexed structure becomes buried when no ligand is present. Moreover, an anti-correlation exists between burial of PTS1 and the size of the binding pocket. The results are in accordance with plant nsLTPs, where a similar accommodation of binding pocket size was found after ligand binding/removal. Furthermore, the calculations support the suggestion of a ligand-assisted targeting mechanism. © 2002 Elsevier Science Ltd. All rights reserved.