PDBsum entry 1zlg

Hormone/growth factor

PDB id: 1zlg

Contents

Protein chain

680 a.a.* *

* Residue conservation analysis

* C-alpha coords only

PDB id:

1zlg

Name:

Hormone/growth factor

Title:

Solution structure of the extracellular matrix protein anosmin-1

Structure:

Anosmin 1. Chain: a. Synonym: kallmann syndrome protein, adhesion molecule-like x-linked. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: kal1, admlx, kal, kalig1. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227.

Authors:

Y.Hu,Z.Sun,J.T.Eaton,P.M.Bouloux,S.J.Perkins

Key ref:

Y.Hu et al. (2005). Extended and flexible domain solution structure of the extracellular matrix protein anosmin-1 by X-ray scattering, analytical ultracentrifugation and constrained modelling. J Mol Biol, 350, 553-570. PubMed id: 15949815 DOI: 10.1016/j.jmb.2005.04.031

Date:

06-May-05 Release date: 09-May-06

Protein chain

P23352  (KALM_HUMAN) -  Anosmin-1 from Homo sapiens

Seq: 680 a.a.

Struc: 680 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.jmb.2005.04.031

J Mol Biol 350:553-570 (2005)

PubMed id: 15949815

Extended and flexible domain solution structure of the extracellular matrix protein anosmin-1 by X-ray scattering, analytical ultracentrifugation and constrained modelling.

Y.Hu, Z.Sun, J.T.Eaton, P.M.Bouloux, S.J.Perkins.

ABSTRACT

Kallmann's syndrome corresponds to a loss of sense of smell and hypogonadotrophic hypogonadism. Defects in anosmin-1 result in the X-linked inherited form of Kallmann's syndrome. Anosmin-1 is an extracellular matrix protein comprised of an N-terminal, cysteine-rich (Cys-box) domain and a whey acidic protein-like (WAP) domain, followed by four fibronectin type III (FnIII) domains. The solution structures of recombinant proteins containing the first three domains (PIWF1) and all six domains (PIWF4) were determined by X-ray scattering and analytical ultracentrifugation. Guinier analyses showed that PIWF1 and PIWF4 have different radii of gyration (R(G)) values of 3.1 nm and 6.7 nm, respectively, but similar cross-sectional radii of gyration (R(XS)) values of 1.5 nm and 1.9 nm, respectively. Distance distribution functions showed that the maximum lengths of PIWF1 and PIWF4 were 11 nm and 23 nm, respectively. Analytical ultracentrifugation gave sedimentation coefficients of 2.52 S and 3.55 S for PIWF1 and PIWF4, respectively. The interpretation of the scattering data by constrained modelling requires homology models for all six domains in anosmin-1. While models were already available for the WAP and FnIII domains, searches suggested the Cys-box domain may resemble the cysteine-rich region of the insulin-like growth factor receptor. Automated constrained molecular modelling based on joining the anosmin-1 domains with structurally randomised linkers resulted in 10,000 models for anosmin-1. A trial-and-error search showed that about 0.1-1.4% of these models fitted the X-ray data. The best models showed that the three domains and six domains in PIWF1 and PIWF4, respectively, were extended. The inter-domain linkers in anosmin-1 could not all be extended at the same time, and there was evidence for inter-domain flexibility. Models with folded-back domain arrangements do not fit the data. These solution structures account for the known biological function of anosmin-1, in particular its ability to interact with its three macromolecular ligands.

Selected figure(s)

Figure 4.
Figure 4. Distance distribution functions P(r) for (a) PIWF1 and (b) PIWF4. The maximum of the P(r) curve is denoted by M, the most frequently occurring distance within PIWF1 and PIWF4. The maximum dimension of PIWF1 and PIWF4 is denoted by L where the P(r) curve intersects P(r)=0.

Figure 6.
Figure 6. Sedimentation velocity fits for PIWF1 and PIWF4. Ten scans recorded at eight minute intervals were recorded using (a) absorbance at 280 nm and (b) interference optics. In (a) and (b), a rotor speed of 35,000 rpm was used for PIWF1 at 1.12 mg/ml. In (c), a rotor speed of 25,000 rpm was used for PIWF4 at 0.32 mg/ml. All 200 scans were used in the fit, but only every tenth scan is shown for clarity. Analysis gave s^o[20,w] values of (a) and (b) 2.46 S and 2.32 S for PIWF1 from the DCDT+ program at the peak position of the g(s*) distributions (arrowed), and (c) 3.80 S for PIWF4 from the SEDFIT program. The circles represent the experimental data and the continuous lines represent the fits to these.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 350, 553-570) copyright 2005.

Figures were selected by an automated process.