1l3h
From Proteopedia
NMR structure of P41icf, a potent inhibitor of human cathepsin L
Structural highlights
Disease[HG2A_HUMAN] Note=A chromosomal aberration involving CD74 is found in a non-small cell lung tumor. Results in the formation of a CD74-ROS1 chimeric protein.[1] Function[HG2A_HUMAN] Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe total synthesis and structural characterization of the MHCII-associated p41 invariant chain fragment (P41icf) is described. P41icf plays a crucial role in the maturation of MHC class II molecules and antigen processing, acting as a highly selective cathepsin L inhibitor. P41icf synthesis was achieved using a combined solid-phase/solution approach. The entire molecule (65 residues, 7246 Da unprotected) was assembled in solution from fully protected peptides in the size range of 10 residues. After deprotection, oxidative folding in carefully adjusted experimental conditions led to the completely folded and functional P41icf with a disulfide pairing identical to that of native P41icf. CD, NMR, and surface plasmon resonance (SPR) were used for the structural and functional characterization of synthetic P41icf. CD thermal denaturation showed clear cooperative behavior. Tight cathepsin L binding was demonstrated by SPR. (1)H NMR spectroscopy at 800 MHz of unlabeled P41icf was used to solve the three-dimensional structure of the molecule. P41icf behaves as a well-folded protein domain with a topology very close to the crystallographic cathepsin L-bound form. Synthesis and NMR structure of p41icf, a potent inhibitor of human cathepsin L.,Chiva C, Barthe P, Codina A, Gairi M, Molina F, Granier C, Pugniere M, Inui T, Nishio H, Nishiuchi Y, Kimura T, Sakakibara S, Albericio F, Giralt E J Am Chem Soc. 2003 Feb 12;125(6):1508-17. PMID:12568610[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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