Structural highlights
Publication Abstract from PubMedVery few studies have attributed a direct, active, functional role to N-linked glycans. We describe here an N-linked glycan with a unique role for maintaining the active conformation of a protein of the serpin family. The distinguishing feature of serpins is the "stressed-to-relaxed" transition, in which the reactive center loop inserts as a beta-strand into the central beta-sheet A. This transition forms the basis for the conversion of serpins to the inactive latent state. We demonstrate that plasminogen activator inhibitor-1 (PAI-1) from zebrafish converts to the latent state about 5-fold slower than human PAI-1. In contrast to human PAI-1, fish PAI-1 carries a single N-linked glycan at Asn185 in the gate region through which the reactive center loop passes during latency transition. While the latency transition of human PAI-1 is unaffected by deglycosylation, deglycosylated zebrafish PAI-1 (zfPAI-1) goes latent about 50-fold faster than the glycosylated zfPAI-1 and about 25-fold faster than non-glycosylated human PAI-1. X-ray crystal structure analysis of glycosylated fish PAI-1 confirmed the presence of an N-linked glycan in the gate region and a lack of glycan-induced structural changes. Thus, latency transition of zfPAI-1 is delayed by steric hindrance from the glycan in the gate region. Our findings reveal a previously unknown mechanism for inhibition of protein conformational changes by steric hindrance from N-linked glycans. Protein conformational change delayed by steric hindrance from an N-linked glycan.,Bager R, Johansen JS, Jensen JK, Stensballe A, Jendroszek A, Buxbom L, Sorensen HP, Andreasen PA J Mol Biol. 2013 Aug 23;425(16):2867-77. doi: 10.1016/j.jmb.2013.05.007. Epub, 2013 May 20. PMID:23702291[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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