Structural highlights
Function
[GROA_HUMAN] Has chemotactic activity for neutrophils. May play a role in inflammation and exerts its effects on endothelial cells in an autocrine fashion. In vitro, the processed forms GRO-alpha(4-73), GRO-alpha(5-73) and GRO-alpha(6-73) show a 30-fold higher chemotactic activity.[1] [2]
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 PubMed
The three-dimensional solution structure of the growth-related protein-alpha/melanoma growth stimulatory activity (GRO/MGSA) has been solved by two-dimensional 1H nuclear magnetic resonance spectroscopy. The GRO/MGSA monomer consists of an NH2-terminal loop, a three-stranded antiparallel beta-sheet, and a COOH-terminal alpha-helix. Dimerization, which is apparent under the experimental conditions used (2 mM, pH 5.10, 30 degrees C), results in a six-stranded antiparallel beta-sheet and a pair of helices with 2-fold symmetry. While the basic fold is similar to that seen for interleukin-8 (IL-8) (Clore, G. M., Appella, E., Yamada, M., Matsushima, K., and Gronenborn, A. M. (1990) Biochemistry, 29, 1689-1696), there are differences in the ELR motif (residues 6-8), the turn involving residues 31-36, which is linked to the NH2-terminal region through the 9-35 disulfide bond. The most significant differences are in the NH2-terminal loop (residues 12-23). In IL-8, all the corresponding regions have been shown to be required for receptor binding (Clark-Lewis, I., Dewald, B., Loetscher, M., Moser, B., and Baggiolini, M. (1994) J. Biol. Chem. 269, 16075-16081). The structural differences thus have been identified between GRO/MGSA and IL-8 could contribute to their different receptor binding specificities.
Solution structure of GRO/melanoma growth stimulatory activity determined by 1H NMR spectroscopy.,Kim KS, Clark-Lewis I, Sykes BD J Biol Chem. 1994 Dec 30;269(52):32909-15. PMID:7806518[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wuyts A, Govaerts C, Struyf S, Lenaerts JP, Put W, Conings R, Proost P, Van Damme J. Isolation of the CXC chemokines ENA-78, GRO alpha and GRO gamma from tumor cells and leukocytes reveals NH2-terminal heterogeneity. Functional comparison of different natural isoforms. Eur J Biochem. 1999 Mar;260(2):421-9. PMID:10095777
- ↑ Wen DZ, Rowland A, Derynck R. Expression and secretion of gro/MGSA by stimulated human endothelial cells. EMBO J. 1989 Jun;8(6):1761-6. PMID:2670560
- ↑ Kim KS, Clark-Lewis I, Sykes BD. Solution structure of GRO/melanoma growth stimulatory activity determined by 1H NMR spectroscopy. J Biol Chem. 1994 Dec 30;269(52):32909-15. PMID:7806518
