1H02

Human Insulin-like growth factor; SRS Daresbury data

Summary for 1H02

• Entry DOI: 10.2210/pdb1h02/pdb
• Related: 1GZR 1GZY 1GZZ 1H59 1IMX 2GF1 3GF1
• Descriptor: INSULIN-LIKE GROWTH FACTOR I, N-DODECYL-N,N-DIMETHYL-3-AMMONIO-1-PROPANESULFONATE (3 entities in total)
• Functional Keywords: cell adhesion, growth factor, insulin family, igf-1, plasma
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 8000.31

Authors

Brzozowski, A.M.,Dodson, E.J.,Dodson, G.G.,Murshudov, G.,Verma, C.,Turkenburg, J.P.,De Bree, F.M.,Dauter, Z. (deposition date: 2002-06-11, release date: 2002-07-25, Last modification date: 2023-12-13)

Primary citation

Brzozowski, A.M.,Dodson, E.J.,Dodson, G.G.,Murshudov, G.,Verma, C.,Turkenburg, J.P.,De Bree, F.M.,Dauter, Z.
Structural Origins of the Functional Divergence of Human Insulin-Like Growth Factor-I and Insulin
Biochemistry, 41:9389-, 2002

PubMed Abstract: Human insulin-like growth factors I and II (hIGF-I, hIGF-II) are potent stimulators of cell and growth processes. They display high sequence similarity to both the A and B chains of insulin but contain an additional connecting C-domain, which reflects their secretion without specific packaging or precursor conversion. IGFs also have an extension at the C-terminus known as the D-domain. This paper describes four homologous hIGF-1 structures, obtained from crystals grown in the presence of the detergent SB12, which reveal additional detail in the C- and D-domains. Two different detergent binding modes observed in the crystals may reflect different hIGF-I biological properties such as the interaction with IGF binding proteins and self-aggregation. While the helical core of hIGF-I is very similar to that in insulin, there are distinct differences in the region of hIGF-I corresponding to the insulin B chain C-terminus, residues B25-B30. In hIGF-I, these residues (24-29) and the following C-domain form an extensive loop protruding 20 A from the core, which results in a substantially different conformation for the receptor binding epitope in hIGF-I compared to insulin. One notable feature of the structures presented here is demonstration of peptide-bond cleavage between Ser35 and Arg36 resulting in an apparent gap between residues 35 and 39. The equivalent region of proinsulin is involved in hormone processing demanding a reassessment of the structural integrity of hIGF-I in relation to its biological function.

PubMed: 12135360
DOI: 10.1021/BI020084J

Experimental method

X-RAY DIFFRACTION (2 Å)