6bg6

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Crystal structure of S111A mutant of human macrophage migration inhibitory factor

Structural highlights

6bg6 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.52Å
Ligands:GOL, IPA, SO4
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MIF_HUMAN Genetic variations in MIF are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.

Function

MIF_HUMAN Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.[1] [2]

Publication Abstract from PubMed

Macrophage migration inhibitory factor (MIF) activates CD74, which leads to severe disorders including inflammation, autoimmune diseases and cancer under pathological conditions. Molecular dynamics (MD) simulations up to one microsecond revealed dynamical correlation between a residue located at the opening of one end of the MIF solvent channel, previously thought to be a consequence of homotrimerization, and residues in a distal region responsible for CD74 activation. Experiments verified the allosteric regulatory site and identified a pathway to this site via the MIF beta-strands. The reported findings provide fundamental insights on a dynamic mechanism that controls the MIF-induced activation of CD74.

Nanosecond Dynamics Regulate the MIF-Induced Activity of CD74.,Pantouris G, Ho J, Shah D, Syed MA, Leng L, Bhandari V, Bucala R, Batista VS, Loria JP, Lolis EJ Angew Chem Int Ed Engl. 2018 Apr 18. doi: 10.1002/anie.201803191. PMID:29669180[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
1 reviews cite this structure
Molecular Level Insights Into the Structural and Dynamic Factors Driving Cytokine Function.
Cui et al. (2021)
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13 other articles
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See Also

References

  1. ↑ Oddo M, Calandra T, Bucala R, Meylan PR. Macrophage migration inhibitory factor reduces the growth of virulent Mycobacterium tuberculosis in human macrophages. Infect Immun. 2005 Jun;73(6):3783-6. PMID:15908412 doi:10.1128/IAI.73.6.3783-3786.2005
  2. ↑ Emonts M, Sweep FC, Grebenchtchikov N, Geurts-Moespot A, Knaup M, Chanson AL, Erard V, Renner P, Hermans PW, Hazelzet JA, Calandra T. Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis. Clin Infect Dis. 2007 May 15;44(10):1321-8. Epub 2007 Apr 5. PMID:17443469 doi:10.1086/514344
  3. ↑ Pantouris G, Ho J, Shah D, Syed MA, Leng L, Bhandari V, Bucala R, Batista VS, Loria JP, Lolis EJ. Nanosecond Dynamics Regulate the MIF-Induced Activity of CD74. Angew Chem Int Ed Engl. 2018 Apr 18. doi: 10.1002/anie.201803191. PMID:29669180 doi:http://dx.doi.org/10.1002/anie.201803191

Contents


PDB ID 6bg6

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