Retraction of JBC heparan paper shows much to like

jcb726coverWe have knocked the Journal of Biological Chemistry in the past for what we believed to be needless — and unhelpful — obfuscation. And more recently, we have praised the journal for taking what we believe to be positive steps in the direction of greater transparency.

Here, again, we come not to bury JBC but to praise it.

The journal has issued a retraction for a 2011 article by a group of researchers in London, England, led by Stephen Perkins. The paper, “The solution structure of heparan sulfate differs from that of heparin,” purported to show that:

The highly sulfated polysaccharides heparin and heparan sulfate (HS) play key roles in the regulation of physiological and pathophysiological processes. Despite its importance, no molecular structures of free HS have been reported up to now. By combining analytical ultracentrifugation, small angle x-ray scattering, and constrained scattering modeling recently used for heparin, we have analyzed the solution structures for eight purified HS fragments degree of polymerization 6-18 (dp6-dp18) and dp24, corresponding to the predominantly unsulfated GlcA-GlcNAc domains of heparan sulfate. Unlike heparin, the sedimentation coefficient s(20,)(w) of HS dp6-dp24 showed a small rotor speed dependence, where similar s(20,)(w) values of 0.82-1.26 S (absorbance optics) and 1.05-1.34 S (interference optics) were determined. The corresponding x-ray scattering measurements of HS dp6-dp24 gave radius of gyration (R(G)) values from 1.03 to 2.82 nm, cross-sectional radius of gyration (R(XS)) values from 0.31 to 0.65 nm, and maximum lengths (L) from 3.0 to 10.0 nm. These data showed that HS has a longer and more bent structure than heparin. Constrained scattering modeling starting from 5000-8000 conformationally randomized HS structures gave best fit dp6-dp16 molecular structures that were longer and more bent than their equivalents in heparin. No fits were obtained for HS dp18 or dp24, indicating their higher flexibility. We conclude that HS displays an extended bent conformation that is significantly distinct from that for heparin. The difference is attributed to the different predominant monosaccharide sequence and reduced sulfation of HS, indicating that HS may interact differently with proteins compared with heparin.

Trouble is, that doesn’t appear to be so — at least, not in the way the researchers initially reported. According to the withdrawal notice:

This article has been withdrawn at the request of the authors.

We determined solution structures for six forms of heparan sulfate dp6–dp16 in this article. Following publication of our 2011 study, we regrettably discovered an error in the anomeric configuration of our heparan sulfate structural models. Correction of this error requires substantial reinterpretation of our experimental data. We wish to withdraw the manuscript and will submit a corrected report. We apologize for any inconvenience caused by this error.

We have asked Perkins for more information on the nature of the glitch and will update this post if we hear from him. The paper has been cited 13 times, according to Thomson Scientific’s Web of Knowledge.

Here’s why we like this retraction notice: Until very recently, JBC notices typically said nothing at all about why a paper was being retracted. We’d get one line notices, along the lines of “This article has been withdrawn by the authors.” Then, the journal started adding relevant information when there had been a finding of misconduct by the Office of Research Integrity, after hiring a manager of publication ethics. And now, it appears they’ll add reasons when an author provides them.

The JBC isn’t quite where we’d want them yet. But these are important steps — and we urge the JBC to continue in this direction, until all of their notices are as clear as possible.

0 thoughts on “Retraction of JBC heparan paper shows much to like”

  1. Pardon me if I misinterpret things; the structure of heparan is well outside my field of expertise.

    Was this paper withdrawn only for an error, even if a fairly pervasive one? Is that appropriate? Won’t retracting the paper obscure the nature of the error, so that others might be tempted to fall into the same trap? Should we reserve retraction for malfeasance? In the not-so-distant past, weren’t scientific errors corrected in a follow-up paper, without the need for a retraction?

    In short: What should be the purpose of a retraction?

    1. Although I have not studied this case in detail, the retraction notice mentions “… an error in the anomeric configuration of our heparan sulfate structural models.” This means that the model the authors (prepared and) studied was in fact not heparan sulfate. Anomeric configuration in polysaccharides is very important and changing it can drastically alter the properties of the polysaccharide. For instance, starch and cellulose are both polymers of D-glucose; they differ only in the anomeric configuration.

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