3lri
From Proteopedia
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SOLUTION STRUCTURE AND BACKBONE DYNAMICS OF HUMAN LONG-[ARG3]INSULIN-LIKE GROWTH FACTOR 1
Contents |
Overview
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.
Disease
Known disease associated with this structure: Growth retardation with deafness and mental retardation due to IGF1 deficiency OMIM:[147440]
About this Structure
3LRI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure and backbone dynamics of long-[Arg(3)]insulin-like growth factor-I., Laajoki LG, Francis GL, Wallace JC, Carver JA, Keniry MA, J Biol Chem. 2000 Apr 7;275(14):10009-15. PMID:10744677
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