3LRI

Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I

Summary for 3LRI

• Entry DOI: 10.2210/pdb3lri/pdb
• NMR Information: BMRB: 4494
• Descriptor: PROTEIN (INSULIN-LIKE GROWTH FACTOR I) (1 entity in total)
• Functional Keywords: insulin-like growth factor-1, growth factor, protein structure, distance geometry
• Biological source: Homo sapiens
• Cellular location: Secreted : P05019
• Total number of polymer chains: 1
• Total formula weight: 9133.61

Authors

Laajoki, L.G.,Francis, G.L.,Wallace, J.C.,Carver, J.A.,Keniry, M.A. (deposition date: 1999-04-13, release date: 2000-05-23, Last modification date: 2024-10-30)

Primary citation

Laajoki, L.G.,Francis, G.L.,Wallace, J.C.,Carver, J.A.,Keniry, M.A.
Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I
J.Biol.Chem., 275:10009-10015, 2000

PubMed Abstract: Long-[Arg(3)]insulin-like growth factor-I (IGF-I) is a potent analog of insulin-like growth factor-I that has been modified by a Glu(3) --> Arg mutation and a 13-amino acid extension appended to the N terminus. We have determined the solution structure of (15)N-labeled Long-[Arg(3)]-IGF-I using high resolution NMR and restrained molecular dynamics techniques to a precision of 0.82 +/- 0.28 A root mean square deviation for the backbone heavy atoms in the three alpha-helices and 3.5 +/- 0.9 A root mean square deviation for all backbone heavy atoms excluding the 8 N-terminal residues and the 8 C-terminal eight residues. Overall, the structure of the IGF-I domain is consistent with earlier studies of IGF-I with some minor changes remote from the N terminus. The major variations in the structure, compared with IGF-I, occur at the N terminus with a substantial reorientation of the N-terminal three residues of the IGF-I domain. These results are interpreted in terms of the lower binding affinity for insulin-like growth factor-binding proteins. The backbone dynamics of Long-[Arg(3)]IGF-I were investigated using (15)N nuclear spin relaxation and the heteronuclear nuclear Overhauser enhancement (NOE). There is a considerable degree of flexibility in Long-[Arg(3)]IGF-I, even in the alpha-helices, as indicated by an average ((1)H)(15)N NOE of 0.55 for the regions. The largest heteronuclear NOEs are observed in the helical regions, lower heteronuclear NOEs are observed in the C-domain loop separating helix 1 from helix 2, and negative heteronuclear NOEs are observed in the N-terminal extension and at the C terminus. Despite these data indicating conformational flexibility for the N-terminal extension, slow amide proton exchange was observed for some residues in this region, suggesting some transitory structure does exist, possibly a molten helix. A certain degree of flexibility may be necessary in all insulin-like growth factors to enable association with various receptors and binding proteins.

PubMed: 10744677
DOI: 10.1074/jbc.275.14.10009

Experimental method

SOLUTION NMR